Immunotherapy

A new tool specifically designed to evaluate immune checkpoint inhibitor–related toxicity, developed based on direct patient involvement, picks up on cutaneous and other side effects that would be missed using traditional quality of life questionnaires, investigators say.

The 25-item list represents the first-ever health-related quality of life (HRQOL) toxicity subscale developed for patients receiving checkpoint inhibitors, according to the investigators, led by Aaron R. Hansen, MBBS, of the division of medical oncology and hematology in the department of medicine at the University of Toronto.

The toxicity subscale is combined with the Functional Assessment of Cancer Therapy–General (FACT-G), which measures physical, emotional, family and social, and functional domains, to form the Functional Assessment of Cancer Therapy–Immune Checkpoint Modulator (FACT-ICM), Dr. Hansen stated in a recent report that describes initial development and early validation efforts.

The FACT-ICM could become an important tool for measuring HRQOL in patients receiving checkpoint inhibitors, depending on results of further investigations including more patients, the authors wrote in that report.

“Currently, we would recommend that our toxicity subscale be validated first before use in clinical care, or in trials with QOL as a primary or secondary endpoint,” wrote Dr. Hansen and colleagues in the report, which appears in Cancer.

The toxicity subscale asks patients to rate items such as “I am bothered by dry skin,” “I feel pain, soreness or aches in some of my muscles,” and “My fatigue keeps me from doing the things I want do” on a scale of 0 (not at all) to 4 (very much).

Development of the toxicity subscale was based on focus groups and interviews with 37 patients with a variety of cancer types who were being treated with a PD-1, PD-L1, and CTLA-4 immune checkpoint inhibitors. Sixteen physicians were surveyed to evaluate the patient input, while 11 of them also participated in follow-up interviews.

“At every step in this process, the patients were central,” the investigators wrote in their report.

According to the investigators, that approach is in line with guidance from the Food and Drug Administration, which has said that meaningful patient input should be used in the upfront development of patient-reported outcome (PRO) measures, rather than obtaining patient endorsement after the fact.

By contrast, an electronic PRO immune-oncology module recently developed, based on 19 immune-related adverse events from drug labels and clinical trial reports, had “no evaluation” of effects on HRQOL, according to Dr. Hansen and coauthors, who added that the tool “did not adhere” to the FDA call for meaningful patient input.

Some previous studies of quality of life in immune checkpoint inhibitor–treated patients have used tumor-specific PROs and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 Items (EORTC-QLQ-C30).

The new, immune checkpoint inhibitor–specific toxicity subscale has “broader coverage” of side effects that reportedly affect HRQOL in patients treated with these agents, including taste disturbance, cough, and fever or chills, according to the investigators.

Moreover, the EORTC-QLQ-C30 and the EORTC head and neck cancer–specific-35 module (EORTC QLQ-H&N35), do not include items related to cutaneous adverse events such as itch, rash, and dry skin that have been seen in some checkpoint inhibitor clinical trials, they noted.

“This represents a clear limitation of such preexisting PRO instruments, which should be addressed with our immune checkpoint moduator–specific tool,” they wrote.

The study was supported by a grant from the University of Toronto. Authors of the study provided disclosures related to Merck, Bristol-Myers Squibb, Karyopharm, Boston Biomedical, Novartis, Genentech, Hoffmann La Roche, GlaxoSmithKline, and others.

SOURCE: Hansen AR et al. Cancer. 2020 Jan 8. doi: 10.1002/cncr.32692.

A new tool specifically designed to evaluate immune checkpoint inhibitor–related toxicity, developed based on direct patient involvement, picks up on cutaneous and other side effects that would be missed using traditional quality of life questionnaires, investigators say.

The 25-item list represents the first-ever health-related quality of life (HRQOL) toxicity subscale developed for patients receiving checkpoint inhibitors, according to the investigators, led by Aaron R. Hansen, MBBS, of the division of medical oncology and hematology in the department of medicine at the University of Toronto.

The toxicity subscale is combined with the Functional Assessment of Cancer Therapy–General (FACT-G), which measures physical, emotional, family and social, and functional domains, to form the Functional Assessment of Cancer Therapy–Immune Checkpoint Modulator (FACT-ICM), Dr. Hansen stated in a recent report that describes initial development and early validation efforts.

The FACT-ICM could become an important tool for measuring HRQOL in patients receiving checkpoint inhibitors, depending on results of further investigations including more patients, the authors wrote in that report.

“Currently, we would recommend that our toxicity subscale be validated first before use in clinical care, or in trials with QOL as a primary or secondary endpoint,” wrote Dr. Hansen and colleagues in the report, which appears in Cancer.

The toxicity subscale asks patients to rate items such as “I am bothered by dry skin,” “I feel pain, soreness or aches in some of my muscles,” and “My fatigue keeps me from doing the things I want do” on a scale of 0 (not at all) to 4 (very much).

Development of the toxicity subscale was based on focus groups and interviews with 37 patients with a variety of cancer types who were being treated with a PD-1, PD-L1, and CTLA-4 immune checkpoint inhibitors. Sixteen physicians were surveyed to evaluate the patient input, while 11 of them also participated in follow-up interviews.

“At every step in this process, the patients were central,” the investigators wrote in their report.

According to the investigators, that approach is in line with guidance from the Food and Drug Administration, which has said that meaningful patient input should be used in the upfront development of patient-reported outcome (PRO) measures, rather than obtaining patient endorsement after the fact.

By contrast, an electronic PRO immune-oncology module recently developed, based on 19 immune-related adverse events from drug labels and clinical trial reports, had “no evaluation” of effects on HRQOL, according to Dr. Hansen and coauthors, who added that the tool “did not adhere” to the FDA call for meaningful patient input.

Some previous studies of quality of life in immune checkpoint inhibitor–treated patients have used tumor-specific PROs and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 Items (EORTC-QLQ-C30).

The new, immune checkpoint inhibitor–specific toxicity subscale has “broader coverage” of side effects that reportedly affect HRQOL in patients treated with these agents, including taste disturbance, cough, and fever or chills, according to the investigators.

Moreover, the EORTC-QLQ-C30 and the EORTC head and neck cancer–specific-35 module (EORTC QLQ-H&N35), do not include items related to cutaneous adverse events such as itch, rash, and dry skin that have been seen in some checkpoint inhibitor clinical trials, they noted.

“This represents a clear limitation of such preexisting PRO instruments, which should be addressed with our immune checkpoint moduator–specific tool,” they wrote.

The study was supported by a grant from the University of Toronto. Authors of the study provided disclosures related to Merck, Bristol-Myers Squibb, Karyopharm, Boston Biomedical, Novartis, Genentech, Hoffmann La Roche, GlaxoSmithKline, and others.

SOURCE: Hansen AR et al. Cancer. 2020 Jan 8. doi: 10.1002/cncr.32692.

A new tool specifically designed to evaluate immune checkpoint inhibitor–related toxicity, developed based on direct patient involvement, picks up on cutaneous and other side effects that would be missed using traditional quality of life questionnaires, investigators say.

The 25-item list represents the first-ever health-related quality of life (HRQOL) toxicity subscale developed for patients receiving checkpoint inhibitors, according to the investigators, led by Aaron R. Hansen, MBBS, of the division of medical oncology and hematology in the department of medicine at the University of Toronto.

The toxicity subscale is combined with the Functional Assessment of Cancer Therapy–General (FACT-G), which measures physical, emotional, family and social, and functional domains, to form the Functional Assessment of Cancer Therapy–Immune Checkpoint Modulator (FACT-ICM), Dr. Hansen stated in a recent report that describes initial development and early validation efforts.

The FACT-ICM could become an important tool for measuring HRQOL in patients receiving checkpoint inhibitors, depending on results of further investigations including more patients, the authors wrote in that report.

“Currently, we would recommend that our toxicity subscale be validated first before use in clinical care, or in trials with QOL as a primary or secondary endpoint,” wrote Dr. Hansen and colleagues in the report, which appears in Cancer.

The toxicity subscale asks patients to rate items such as “I am bothered by dry skin,” “I feel pain, soreness or aches in some of my muscles,” and “My fatigue keeps me from doing the things I want do” on a scale of 0 (not at all) to 4 (very much).

Development of the toxicity subscale was based on focus groups and interviews with 37 patients with a variety of cancer types who were being treated with a PD-1, PD-L1, and CTLA-4 immune checkpoint inhibitors. Sixteen physicians were surveyed to evaluate the patient input, while 11 of them also participated in follow-up interviews.

“At every step in this process, the patients were central,” the investigators wrote in their report.

According to the investigators, that approach is in line with guidance from the Food and Drug Administration, which has said that meaningful patient input should be used in the upfront development of patient-reported outcome (PRO) measures, rather than obtaining patient endorsement after the fact.

By contrast, an electronic PRO immune-oncology module recently developed, based on 19 immune-related adverse events from drug labels and clinical trial reports, had “no evaluation” of effects on HRQOL, according to Dr. Hansen and coauthors, who added that the tool “did not adhere” to the FDA call for meaningful patient input.

Some previous studies of quality of life in immune checkpoint inhibitor–treated patients have used tumor-specific PROs and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 Items (EORTC-QLQ-C30).

The new, immune checkpoint inhibitor–specific toxicity subscale has “broader coverage” of side effects that reportedly affect HRQOL in patients treated with these agents, including taste disturbance, cough, and fever or chills, according to the investigators.

Moreover, the EORTC-QLQ-C30 and the EORTC head and neck cancer–specific-35 module (EORTC QLQ-H&N35), do not include items related to cutaneous adverse events such as itch, rash, and dry skin that have been seen in some checkpoint inhibitor clinical trials, they noted.

“This represents a clear limitation of such preexisting PRO instruments, which should be addressed with our immune checkpoint moduator–specific tool,” they wrote.

The study was supported by a grant from the University of Toronto. Authors of the study provided disclosures related to Merck, Bristol-Myers Squibb, Karyopharm, Boston Biomedical, Novartis, Genentech, Hoffmann La Roche, GlaxoSmithKline, and others.

SOURCE: Hansen AR et al. Cancer. 2020 Jan 8. doi: 10.1002/cncr.32692.

ORLANDO – Anti-CD5 chimeric antigen receptor (CAR) T cells can produce complete responses (CRs) in patients with relapsed or refractory T-cell malignancies, according to findings from a phase 1 trial.

Jennifer Smith/MDedge News

Three of 11 patients achieved a CR after CAR T-cell therapy, and one patient achieved a mixed response that deepened to a CR after transplant. Three responders, all of whom had T-cell lymphoma, were still alive and in CR at last follow-up.

There were no cases of severe cytokine release syndrome (CRS) or severe neurotoxicity, no serious infectious complications, and no nonhematologic grade 4 adverse events in this trial.

LaQuisa C. Hill, MD, of Baylor College of Medicine, Houston, presented these results at the annual meeting of the American Society of Hematology.

“While CD19 CAR T cells have revolutionized the treatment of relapsed/refractory B-cell malignancies, development of CAR T-cell platforms targeting T-cell-driven malignancies have been hindered by three main factors: CAR T-cell fratricide due to shared expression of target antigens leading to impaired expansion, ablation of normal T cells continuing to cause profound immunodeficiency, and the potential of transduced tumor cells providing a means of tumor escape,” Dr. Hill said.

Researchers have theorized that anti-CD5 CAR T cells can overcome these obstacles. In preclinical studies, anti-CD5 CAR T cells eliminated malignant blasts in vitro and in vivo and resulted in “limited and transient” fratricide (Blood. 2015 Aug 20;126[8]:983-92).

With this in mind, Dr. Hill and her colleagues tested CD5.28z CAR T cells in a phase 1 trial (NCT03081910). Eleven patients have been treated thus far – five with T-cell acute lymphoblastic leukemia (T-ALL), three with peripheral T-cell lymphoma (PTCL), two with angioimmunoblastic T-cell lymphoma (AITL), and one with Sézary syndrome.

The patients’ median age at baseline was 62 years (range, 21-71 years), and 63% were men. They had received a median of 5 prior therapies (range, 3-18). Two patients had relapsed after allogeneic hematopoietic stem cell transplant (HSCT), three had relapsed after autologous HSCT, and five were primary refractory.

Patients underwent lymphodepletion with fludarabine and cyclophosphamide, then received CAR T cells at doses of 1 x 10⁷ or 5 x 10⁷.
 

Response

Three lymphoma patients – two with AITL and one with PTCL – were still alive and in CR at last follow-up. The PTCL patient achieved a CR after CAR T-cell therapy and declined a subsequent HSCT. The patient has not received additional therapy and has retained the CR for 7 months.

One AITL patient achieved a CR and declined transplant as well. He relapsed after 7 months but received subsequent therapy and achieved another CR. The other AITL patient had a mixed response to CAR T-cell therapy but proceeded to allogeneic HSCT and achieved a CR that has lasted 9 months.

The remaining three lymphoma patients – two with PTCL and one with Sézary syndrome – progressed and died.

One T-ALL patient achieved a CR lasting 6 weeks, but the patient died while undergoing transplant workup. Two T-ALL patients did not respond to treatment and died. The remaining two patients progressed, and one of them died. The other patient who progressed is still alive and in CR after receiving subsequent therapy.

Factors associated with response

Dr. Hill said a shortened manufacturing process may be associated with enhanced response, as all responders received CAR T cells produced via a shorter manufacturing process. The shortened process involves freezing cells on day 4-5 post transduction, as opposed to day 7.

“While the numbers are too small to make any definitive conclusions, this seems to correlate with less terminal differentiation, which might improve potency,” Dr. Hill said. “However, additional analyses are ongoing.”

Dr. Hill also pointed out that CAR T-cell expansion was observed in all patients, with higher peak levels observed at the higher dose. In addition, CAR T-cell persistence was durable at both dose levels.

“We have been able to detect the CAR transgene at all follow-up time points, out to 9 months for some patients,” Dr. Hill said. “While limited persistence may play a role in nonresponders, it does not appear to be the only factor.”

Safety

“Surprisingly, no selective ablation of normal T cells has been observed,” Dr. Hill said. “As CAR T cells dwindled [after infusion], we were able to see recovery of normal T cells, all of which expressed normal levels of CD5. This was observed in all patients on study, except for one patient who had prolonged pancytopenia.”

Cytopenias were the most common grade 3/4 adverse events, including neutropenia (n = 8), anemia (n = 7), and thrombocytopenia (n = 5). Other grade 3/4 events included elevated aspartate aminotransferase (n = 2), hypoalbuminemia (n = 1), hyponatremia (n = 1), hypophosphatemia (n = 1), and elevated alanine aminotransferase (n = 1). There were no grade 5 adverse events.

Two patients developed grade 1 CRS, and two had grade 2 CRS. Both patients with grade 2 CRS were treated with tocilizumab, and their symptoms resolved.

One patient developed grade 2 immune effector cell-associated neurotoxicity syndrome, but this resolved with supportive care.

One patient had a central line–associated bloodstream infection (coagulase-negative staphylococci), and one had cytomegalovirus and BK virus reactivation. There were no fungal infections.

“We have demonstrated that CD5 CAR T cells can be manufactured from heavily pretreated patients with T-cell malignancies, and therapy is well tolerated,” Dr. Hill said. “We have seen strong and promising activity in T-cell lymphoma, which we hope to be able to translate to T-ALL as well.”

Dr. Hill said she and her colleagues hope to improve upon these results with a higher dose level of CD5 CAR T cells (1 x 10⁸), which the team plans to start testing soon. The researchers may also investigate other target antigens, such as CD7, as well as the use of donor-derived CAR T cells for patients who have relapsed after allogeneic HSCT.

Dr. Hill said she has no relevant disclosures. Baylor College of Medicine is sponsoring this trial.

jensmith@mdedge.com

SOURCE: Hill L et al. ASH 2019. Abstract 199.

ORLANDO – Anti-CD5 chimeric antigen receptor (CAR) T cells can produce complete responses (CRs) in patients with relapsed or refractory T-cell malignancies, according to findings from a phase 1 trial.

Jennifer Smith/MDedge News

Three of 11 patients achieved a CR after CAR T-cell therapy, and one patient achieved a mixed response that deepened to a CR after transplant. Three responders, all of whom had T-cell lymphoma, were still alive and in CR at last follow-up.

There were no cases of severe cytokine release syndrome (CRS) or severe neurotoxicity, no serious infectious complications, and no nonhematologic grade 4 adverse events in this trial.

LaQuisa C. Hill, MD, of Baylor College of Medicine, Houston, presented these results at the annual meeting of the American Society of Hematology.

“While CD19 CAR T cells have revolutionized the treatment of relapsed/refractory B-cell malignancies, development of CAR T-cell platforms targeting T-cell-driven malignancies have been hindered by three main factors: CAR T-cell fratricide due to shared expression of target antigens leading to impaired expansion, ablation of normal T cells continuing to cause profound immunodeficiency, and the potential of transduced tumor cells providing a means of tumor escape,” Dr. Hill said.

Researchers have theorized that anti-CD5 CAR T cells can overcome these obstacles. In preclinical studies, anti-CD5 CAR T cells eliminated malignant blasts in vitro and in vivo and resulted in “limited and transient” fratricide (Blood. 2015 Aug 20;126[8]:983-92).

With this in mind, Dr. Hill and her colleagues tested CD5.28z CAR T cells in a phase 1 trial (NCT03081910). Eleven patients have been treated thus far – five with T-cell acute lymphoblastic leukemia (T-ALL), three with peripheral T-cell lymphoma (PTCL), two with angioimmunoblastic T-cell lymphoma (AITL), and one with Sézary syndrome.

The patients’ median age at baseline was 62 years (range, 21-71 years), and 63% were men. They had received a median of 5 prior therapies (range, 3-18). Two patients had relapsed after allogeneic hematopoietic stem cell transplant (HSCT), three had relapsed after autologous HSCT, and five were primary refractory.

Patients underwent lymphodepletion with fludarabine and cyclophosphamide, then received CAR T cells at doses of 1 x 10⁷ or 5 x 10⁷.
 

Response

Three lymphoma patients – two with AITL and one with PTCL – were still alive and in CR at last follow-up. The PTCL patient achieved a CR after CAR T-cell therapy and declined a subsequent HSCT. The patient has not received additional therapy and has retained the CR for 7 months.

One AITL patient achieved a CR and declined transplant as well. He relapsed after 7 months but received subsequent therapy and achieved another CR. The other AITL patient had a mixed response to CAR T-cell therapy but proceeded to allogeneic HSCT and achieved a CR that has lasted 9 months.

The remaining three lymphoma patients – two with PTCL and one with Sézary syndrome – progressed and died.

One T-ALL patient achieved a CR lasting 6 weeks, but the patient died while undergoing transplant workup. Two T-ALL patients did not respond to treatment and died. The remaining two patients progressed, and one of them died. The other patient who progressed is still alive and in CR after receiving subsequent therapy.

Factors associated with response

Dr. Hill said a shortened manufacturing process may be associated with enhanced response, as all responders received CAR T cells produced via a shorter manufacturing process. The shortened process involves freezing cells on day 4-5 post transduction, as opposed to day 7.

“While the numbers are too small to make any definitive conclusions, this seems to correlate with less terminal differentiation, which might improve potency,” Dr. Hill said. “However, additional analyses are ongoing.”

Dr. Hill also pointed out that CAR T-cell expansion was observed in all patients, with higher peak levels observed at the higher dose. In addition, CAR T-cell persistence was durable at both dose levels.

“We have been able to detect the CAR transgene at all follow-up time points, out to 9 months for some patients,” Dr. Hill said. “While limited persistence may play a role in nonresponders, it does not appear to be the only factor.”

Safety

“Surprisingly, no selective ablation of normal T cells has been observed,” Dr. Hill said. “As CAR T cells dwindled [after infusion], we were able to see recovery of normal T cells, all of which expressed normal levels of CD5. This was observed in all patients on study, except for one patient who had prolonged pancytopenia.”

Cytopenias were the most common grade 3/4 adverse events, including neutropenia (n = 8), anemia (n = 7), and thrombocytopenia (n = 5). Other grade 3/4 events included elevated aspartate aminotransferase (n = 2), hypoalbuminemia (n = 1), hyponatremia (n = 1), hypophosphatemia (n = 1), and elevated alanine aminotransferase (n = 1). There were no grade 5 adverse events.

Two patients developed grade 1 CRS, and two had grade 2 CRS. Both patients with grade 2 CRS were treated with tocilizumab, and their symptoms resolved.

One patient developed grade 2 immune effector cell-associated neurotoxicity syndrome, but this resolved with supportive care.

One patient had a central line–associated bloodstream infection (coagulase-negative staphylococci), and one had cytomegalovirus and BK virus reactivation. There were no fungal infections.

“We have demonstrated that CD5 CAR T cells can be manufactured from heavily pretreated patients with T-cell malignancies, and therapy is well tolerated,” Dr. Hill said. “We have seen strong and promising activity in T-cell lymphoma, which we hope to be able to translate to T-ALL as well.”

Dr. Hill said she and her colleagues hope to improve upon these results with a higher dose level of CD5 CAR T cells (1 x 10⁸), which the team plans to start testing soon. The researchers may also investigate other target antigens, such as CD7, as well as the use of donor-derived CAR T cells for patients who have relapsed after allogeneic HSCT.

Dr. Hill said she has no relevant disclosures. Baylor College of Medicine is sponsoring this trial.

jensmith@mdedge.com

SOURCE: Hill L et al. ASH 2019. Abstract 199.

ORLANDO – Anti-CD5 chimeric antigen receptor (CAR) T cells can produce complete responses (CRs) in patients with relapsed or refractory T-cell malignancies, according to findings from a phase 1 trial.

Jennifer Smith/MDedge News

Three of 11 patients achieved a CR after CAR T-cell therapy, and one patient achieved a mixed response that deepened to a CR after transplant. Three responders, all of whom had T-cell lymphoma, were still alive and in CR at last follow-up.

There were no cases of severe cytokine release syndrome (CRS) or severe neurotoxicity, no serious infectious complications, and no nonhematologic grade 4 adverse events in this trial.

LaQuisa C. Hill, MD, of Baylor College of Medicine, Houston, presented these results at the annual meeting of the American Society of Hematology.

“While CD19 CAR T cells have revolutionized the treatment of relapsed/refractory B-cell malignancies, development of CAR T-cell platforms targeting T-cell-driven malignancies have been hindered by three main factors: CAR T-cell fratricide due to shared expression of target antigens leading to impaired expansion, ablation of normal T cells continuing to cause profound immunodeficiency, and the potential of transduced tumor cells providing a means of tumor escape,” Dr. Hill said.

Researchers have theorized that anti-CD5 CAR T cells can overcome these obstacles. In preclinical studies, anti-CD5 CAR T cells eliminated malignant blasts in vitro and in vivo and resulted in “limited and transient” fratricide (Blood. 2015 Aug 20;126[8]:983-92).

With this in mind, Dr. Hill and her colleagues tested CD5.28z CAR T cells in a phase 1 trial (NCT03081910). Eleven patients have been treated thus far – five with T-cell acute lymphoblastic leukemia (T-ALL), three with peripheral T-cell lymphoma (PTCL), two with angioimmunoblastic T-cell lymphoma (AITL), and one with Sézary syndrome.

The patients’ median age at baseline was 62 years (range, 21-71 years), and 63% were men. They had received a median of 5 prior therapies (range, 3-18). Two patients had relapsed after allogeneic hematopoietic stem cell transplant (HSCT), three had relapsed after autologous HSCT, and five were primary refractory.

Patients underwent lymphodepletion with fludarabine and cyclophosphamide, then received CAR T cells at doses of 1 x 10⁷ or 5 x 10⁷.
 

Response

Three lymphoma patients – two with AITL and one with PTCL – were still alive and in CR at last follow-up. The PTCL patient achieved a CR after CAR T-cell therapy and declined a subsequent HSCT. The patient has not received additional therapy and has retained the CR for 7 months.

One AITL patient achieved a CR and declined transplant as well. He relapsed after 7 months but received subsequent therapy and achieved another CR. The other AITL patient had a mixed response to CAR T-cell therapy but proceeded to allogeneic HSCT and achieved a CR that has lasted 9 months.

The remaining three lymphoma patients – two with PTCL and one with Sézary syndrome – progressed and died.

One T-ALL patient achieved a CR lasting 6 weeks, but the patient died while undergoing transplant workup. Two T-ALL patients did not respond to treatment and died. The remaining two patients progressed, and one of them died. The other patient who progressed is still alive and in CR after receiving subsequent therapy.

Factors associated with response

Dr. Hill said a shortened manufacturing process may be associated with enhanced response, as all responders received CAR T cells produced via a shorter manufacturing process. The shortened process involves freezing cells on day 4-5 post transduction, as opposed to day 7.

“While the numbers are too small to make any definitive conclusions, this seems to correlate with less terminal differentiation, which might improve potency,” Dr. Hill said. “However, additional analyses are ongoing.”

Dr. Hill also pointed out that CAR T-cell expansion was observed in all patients, with higher peak levels observed at the higher dose. In addition, CAR T-cell persistence was durable at both dose levels.

“We have been able to detect the CAR transgene at all follow-up time points, out to 9 months for some patients,” Dr. Hill said. “While limited persistence may play a role in nonresponders, it does not appear to be the only factor.”

Safety

“Surprisingly, no selective ablation of normal T cells has been observed,” Dr. Hill said. “As CAR T cells dwindled [after infusion], we were able to see recovery of normal T cells, all of which expressed normal levels of CD5. This was observed in all patients on study, except for one patient who had prolonged pancytopenia.”

Cytopenias were the most common grade 3/4 adverse events, including neutropenia (n = 8), anemia (n = 7), and thrombocytopenia (n = 5). Other grade 3/4 events included elevated aspartate aminotransferase (n = 2), hypoalbuminemia (n = 1), hyponatremia (n = 1), hypophosphatemia (n = 1), and elevated alanine aminotransferase (n = 1). There were no grade 5 adverse events.

Two patients developed grade 1 CRS, and two had grade 2 CRS. Both patients with grade 2 CRS were treated with tocilizumab, and their symptoms resolved.

One patient developed grade 2 immune effector cell-associated neurotoxicity syndrome, but this resolved with supportive care.

One patient had a central line–associated bloodstream infection (coagulase-negative staphylococci), and one had cytomegalovirus and BK virus reactivation. There were no fungal infections.

“We have demonstrated that CD5 CAR T cells can be manufactured from heavily pretreated patients with T-cell malignancies, and therapy is well tolerated,” Dr. Hill said. “We have seen strong and promising activity in T-cell lymphoma, which we hope to be able to translate to T-ALL as well.”

Dr. Hill said she and her colleagues hope to improve upon these results with a higher dose level of CD5 CAR T cells (1 x 10⁸), which the team plans to start testing soon. The researchers may also investigate other target antigens, such as CD7, as well as the use of donor-derived CAR T cells for patients who have relapsed after allogeneic HSCT.

Dr. Hill said she has no relevant disclosures. Baylor College of Medicine is sponsoring this trial.

jensmith@mdedge.com

SOURCE: Hill L et al. ASH 2019. Abstract 199.

ORLANDO – Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated manageable toxicity and promising clinical activity in the phase 1 portion of a trial enrolling heavily pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, according to an investigator.

Andrew D. Bowser/MDedge News

The overall response rate exceeded 80%, and most patients in response at 6 months had maintained that response at the 9-month mark, said Tanya Siddiqi, MD, of City of Hope National Medical Center, Duarte, Calif.

“Clinical responses were rapid, improved with time, and were deep and durable,” Dr. Siddiqi said at the annual meeting of the American Society of Hematology.

These findings have provided justification for conducting the phase 2 portion of the study, which is currently enrolling at the higher of two dose levels evaluated in phase 1, she added.

Dr. Siddiqi reported on a total of 23 patients enrolled in the study, known as TRANSCEND CLL 004. All patients had relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and had received at least two prior therapies, including ibrutinib, while about one-third had failed venetoclax as well.

The median patient age was 66 years, and 83% had high-risk features, according to Dr. Siddiqi, who said patients had received a median of five prior lines of therapy.

Nine patients were treated at dose level 1, or 50 x 10⁶ CAR+ T cells, while 14 were treated at dose level 2, or 100 x 10⁶ CAR+ T cells. Two patients experienced grade 3 or 4 dose-limiting toxicities at the second level, including hypertension in one patient, and encephalopathy, muscle weakness, and tumor lysis syndrome (TLS) in the other.

Cytokine release syndrome (CRS) occurred in 17 patients, though only two cases reached grade 3. Neurologic adverse events were seen in nine patients, of which five were grade 3 or 4.

SOURCE: Siddiqi T et al. ASH 2019, Abstract 503.

ORLANDO – Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated manageable toxicity and promising clinical activity in the phase 1 portion of a trial enrolling heavily pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, according to an investigator.

Andrew D. Bowser/MDedge News

The overall response rate exceeded 80%, and most patients in response at 6 months had maintained that response at the 9-month mark, said Tanya Siddiqi, MD, of City of Hope National Medical Center, Duarte, Calif.

“Clinical responses were rapid, improved with time, and were deep and durable,” Dr. Siddiqi said at the annual meeting of the American Society of Hematology.

These findings have provided justification for conducting the phase 2 portion of the study, which is currently enrolling at the higher of two dose levels evaluated in phase 1, she added.

Dr. Siddiqi reported on a total of 23 patients enrolled in the study, known as TRANSCEND CLL 004. All patients had relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and had received at least two prior therapies, including ibrutinib, while about one-third had failed venetoclax as well.

The median patient age was 66 years, and 83% had high-risk features, according to Dr. Siddiqi, who said patients had received a median of five prior lines of therapy.

Nine patients were treated at dose level 1, or 50 x 10⁶ CAR+ T cells, while 14 were treated at dose level 2, or 100 x 10⁶ CAR+ T cells. Two patients experienced grade 3 or 4 dose-limiting toxicities at the second level, including hypertension in one patient, and encephalopathy, muscle weakness, and tumor lysis syndrome (TLS) in the other.

Cytokine release syndrome (CRS) occurred in 17 patients, though only two cases reached grade 3. Neurologic adverse events were seen in nine patients, of which five were grade 3 or 4.

SOURCE: Siddiqi T et al. ASH 2019, Abstract 503.

ORLANDO – Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated manageable toxicity and promising clinical activity in the phase 1 portion of a trial enrolling heavily pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, according to an investigator.

Andrew D. Bowser/MDedge News

The overall response rate exceeded 80%, and most patients in response at 6 months had maintained that response at the 9-month mark, said Tanya Siddiqi, MD, of City of Hope National Medical Center, Duarte, Calif.

“Clinical responses were rapid, improved with time, and were deep and durable,” Dr. Siddiqi said at the annual meeting of the American Society of Hematology.

These findings have provided justification for conducting the phase 2 portion of the study, which is currently enrolling at the higher of two dose levels evaluated in phase 1, she added.

Dr. Siddiqi reported on a total of 23 patients enrolled in the study, known as TRANSCEND CLL 004. All patients had relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and had received at least two prior therapies, including ibrutinib, while about one-third had failed venetoclax as well.

The median patient age was 66 years, and 83% had high-risk features, according to Dr. Siddiqi, who said patients had received a median of five prior lines of therapy.

Nine patients were treated at dose level 1, or 50 x 10⁶ CAR+ T cells, while 14 were treated at dose level 2, or 100 x 10⁶ CAR+ T cells. Two patients experienced grade 3 or 4 dose-limiting toxicities at the second level, including hypertension in one patient, and encephalopathy, muscle weakness, and tumor lysis syndrome (TLS) in the other.

Cytokine release syndrome (CRS) occurred in 17 patients, though only two cases reached grade 3. Neurologic adverse events were seen in nine patients, of which five were grade 3 or 4.

SOURCE: Siddiqi T et al. ASH 2019, Abstract 503.

ORLANDO – A gamma secretase inhibitor could enhance the efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma, a phase 1 trial suggests.

Jennifer Smith/MDedge News

The inhibitor, JSMD194, increased BCMA expression in all 10 patients studied. All patients responded to anti-BCMA CAR T-cell therapy, including three patients who had previously failed BCMA-directed therapy.

Nine patients remain alive and in response at a median follow-up of 20 weeks, with two patients being followed for more than a year. One patient experienced dose-limiting toxicity and died, which prompted a change to the study’s eligibility criteria.

Andrew J. Cowan, MD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, presented these results at the annual meeting of the American Society of Hematology.

Study treatment

Patients had BCMA expression measured at baseline, then underwent apheresis for CAR T-cell production.

Patients received JSMD194 at 25 mg on days 1, 3, and 5. Then, they received cyclophosphamide at 300 mg and fludarabine at 25 mg for 3 days.

Next, patients received a single CAR T-cell infusion at a dose of 50 x 10⁶ (n = 5), 150 x 10⁶ (n = 3), or 300 x 10⁶ (n = 2). They also received JSMD194 at 25 mg three times a week for 3 weeks.

Safety

“Nearly all patients had a serious adverse event, which was typically admission to the hospital for neutropenic fever,” Dr. Cowan said.

One patient experienced dose-limiting toxicity and died at day 33. The patient had a disseminating fungal infection, grade 4 cytokine release syndrome (CRS), and neurotoxicity. The patient’s death prompted the researchers to include performance status in the study’s eligibility criteria.

All patients developed CRS. Only the aforementioned patient had grade 4 CRS, and three patients had grade 3 CRS. Six patients experienced neurotoxicity. There were no cases of tumor lysis syndrome.
 

Efficacy

“All patients experienced an increase of cells expressing BCMA,” Dr. Cowan said. “While there was significant variability in BCMA expression at baseline, all cells expressed BCMA after three doses of the gamma secretase inhibitor.”

The median BCMA expression after JSMD194 treatment was 99% (range, 96%-100%), and there was a median 20-fold (range, 8- to 157-fold) increase in BCMA surface density.

The overall response rate was 100%. Two patients achieved a stringent complete response (CR), one achieved a CR, five patients had a very good partial response, and two had a partial response.

The patient with a CR received the 50 x 10⁶ dose of CAR T cells, and the patients with stringent CRs received the 150 x 10⁶ and 300 x 10⁶ doses.

Of the three patients who previously received BCMA-directed therapy, two achieved a very good partial response, and one had a partial response.

Nine of the 10 patients are still alive and in response, with a median follow-up of 20 weeks. The longest follow-up is 444 days.

“To date, all patients have evidence of durable responses,” Dr. Cowan said. “Moreover, all patients had dramatic reductions in involved serum free light chain ... and serum monoclonal proteins.”

Dr. Cowan noted that longer follow-up is needed to assess CAR T-cell persistence and the durability of response.

This trial is sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. Two researchers involved in this work are employees of Juno Therapeutics. Dr. Cowan reported relationships with Juno Therapeutics, Janssen, Celgene, AbbVie, Cellectar, and Sanofi.

jensmith@mdedge.com

SOURCE: Cowan AJ et al. ASH 2019. Abstract 204.

ORLANDO – A gamma secretase inhibitor could enhance the efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma, a phase 1 trial suggests.

Jennifer Smith/MDedge News

The inhibitor, JSMD194, increased BCMA expression in all 10 patients studied. All patients responded to anti-BCMA CAR T-cell therapy, including three patients who had previously failed BCMA-directed therapy.

Nine patients remain alive and in response at a median follow-up of 20 weeks, with two patients being followed for more than a year. One patient experienced dose-limiting toxicity and died, which prompted a change to the study’s eligibility criteria.

Andrew J. Cowan, MD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, presented these results at the annual meeting of the American Society of Hematology.

Study treatment

Patients had BCMA expression measured at baseline, then underwent apheresis for CAR T-cell production.

Patients received JSMD194 at 25 mg on days 1, 3, and 5. Then, they received cyclophosphamide at 300 mg and fludarabine at 25 mg for 3 days.

Next, patients received a single CAR T-cell infusion at a dose of 50 x 10⁶ (n = 5), 150 x 10⁶ (n = 3), or 300 x 10⁶ (n = 2). They also received JSMD194 at 25 mg three times a week for 3 weeks.

Safety

“Nearly all patients had a serious adverse event, which was typically admission to the hospital for neutropenic fever,” Dr. Cowan said.

One patient experienced dose-limiting toxicity and died at day 33. The patient had a disseminating fungal infection, grade 4 cytokine release syndrome (CRS), and neurotoxicity. The patient’s death prompted the researchers to include performance status in the study’s eligibility criteria.

All patients developed CRS. Only the aforementioned patient had grade 4 CRS, and three patients had grade 3 CRS. Six patients experienced neurotoxicity. There were no cases of tumor lysis syndrome.
 

Efficacy

“All patients experienced an increase of cells expressing BCMA,” Dr. Cowan said. “While there was significant variability in BCMA expression at baseline, all cells expressed BCMA after three doses of the gamma secretase inhibitor.”

The median BCMA expression after JSMD194 treatment was 99% (range, 96%-100%), and there was a median 20-fold (range, 8- to 157-fold) increase in BCMA surface density.

The overall response rate was 100%. Two patients achieved a stringent complete response (CR), one achieved a CR, five patients had a very good partial response, and two had a partial response.

The patient with a CR received the 50 x 10⁶ dose of CAR T cells, and the patients with stringent CRs received the 150 x 10⁶ and 300 x 10⁶ doses.

Of the three patients who previously received BCMA-directed therapy, two achieved a very good partial response, and one had a partial response.

Nine of the 10 patients are still alive and in response, with a median follow-up of 20 weeks. The longest follow-up is 444 days.

“To date, all patients have evidence of durable responses,” Dr. Cowan said. “Moreover, all patients had dramatic reductions in involved serum free light chain ... and serum monoclonal proteins.”

Dr. Cowan noted that longer follow-up is needed to assess CAR T-cell persistence and the durability of response.

This trial is sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. Two researchers involved in this work are employees of Juno Therapeutics. Dr. Cowan reported relationships with Juno Therapeutics, Janssen, Celgene, AbbVie, Cellectar, and Sanofi.

jensmith@mdedge.com

SOURCE: Cowan AJ et al. ASH 2019. Abstract 204.

ORLANDO – A gamma secretase inhibitor could enhance the efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma, a phase 1 trial suggests.

Jennifer Smith/MDedge News

The inhibitor, JSMD194, increased BCMA expression in all 10 patients studied. All patients responded to anti-BCMA CAR T-cell therapy, including three patients who had previously failed BCMA-directed therapy.

Nine patients remain alive and in response at a median follow-up of 20 weeks, with two patients being followed for more than a year. One patient experienced dose-limiting toxicity and died, which prompted a change to the study’s eligibility criteria.

Andrew J. Cowan, MD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, presented these results at the annual meeting of the American Society of Hematology.

Study treatment

Patients had BCMA expression measured at baseline, then underwent apheresis for CAR T-cell production.

Patients received JSMD194 at 25 mg on days 1, 3, and 5. Then, they received cyclophosphamide at 300 mg and fludarabine at 25 mg for 3 days.

Next, patients received a single CAR T-cell infusion at a dose of 50 x 10⁶ (n = 5), 150 x 10⁶ (n = 3), or 300 x 10⁶ (n = 2). They also received JSMD194 at 25 mg three times a week for 3 weeks.

Safety

“Nearly all patients had a serious adverse event, which was typically admission to the hospital for neutropenic fever,” Dr. Cowan said.

One patient experienced dose-limiting toxicity and died at day 33. The patient had a disseminating fungal infection, grade 4 cytokine release syndrome (CRS), and neurotoxicity. The patient’s death prompted the researchers to include performance status in the study’s eligibility criteria.

All patients developed CRS. Only the aforementioned patient had grade 4 CRS, and three patients had grade 3 CRS. Six patients experienced neurotoxicity. There were no cases of tumor lysis syndrome.
 

Efficacy

“All patients experienced an increase of cells expressing BCMA,” Dr. Cowan said. “While there was significant variability in BCMA expression at baseline, all cells expressed BCMA after three doses of the gamma secretase inhibitor.”

The median BCMA expression after JSMD194 treatment was 99% (range, 96%-100%), and there was a median 20-fold (range, 8- to 157-fold) increase in BCMA surface density.

The overall response rate was 100%. Two patients achieved a stringent complete response (CR), one achieved a CR, five patients had a very good partial response, and two had a partial response.

The patient with a CR received the 50 x 10⁶ dose of CAR T cells, and the patients with stringent CRs received the 150 x 10⁶ and 300 x 10⁶ doses.

Of the three patients who previously received BCMA-directed therapy, two achieved a very good partial response, and one had a partial response.

Nine of the 10 patients are still alive and in response, with a median follow-up of 20 weeks. The longest follow-up is 444 days.

“To date, all patients have evidence of durable responses,” Dr. Cowan said. “Moreover, all patients had dramatic reductions in involved serum free light chain ... and serum monoclonal proteins.”

Dr. Cowan noted that longer follow-up is needed to assess CAR T-cell persistence and the durability of response.

This trial is sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. Two researchers involved in this work are employees of Juno Therapeutics. Dr. Cowan reported relationships with Juno Therapeutics, Janssen, Celgene, AbbVie, Cellectar, and Sanofi.

jensmith@mdedge.com

SOURCE: Cowan AJ et al. ASH 2019. Abstract 204.

ORLANDO – Updated results from the TRANSCEND NHL trial include survival data with lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory B-cell lymphomas.

Jennifer Smith/MDedge News

The median progression-free survival (PFS) was 6.8 months, and the median overall survival was 21.1 months. PFS results were best among complete responders and among patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma.

Jeremy S. Abramson, MD, of Massachusetts General Hospital in Boston, presented these results at the annual meeting of the American Society of Hematology.

“TRANSCEND NHL is the largest clinical study to date of CD19-directed CAR T cells in patients with relapsed/refractory aggressive B-cell lymphoma,” Dr. Abramson said.

The phase 1 trial (NCT02631044) includes 269 patients who received liso-cel. They were diagnosed with transformed follicular lymphoma (22%) or other indolent lymphoma (7%), high-grade B-cell lymphoma (13%), primary mediastinal large B-cell lymphoma (6%), grade 3B follicular lymphoma (1%), or diffuse large B-cell lymphoma not otherwise specified (51%).

At baseline, patients had received a median of three prior systemic therapies (range, one to eight). Some patients had received autologous (33%) or allogeneic (3%) transplant. Many patients were chemotherapy refractory (67%) or had never achieved a complete response to prior therapy (44%).

More than half of patients (59%) received bridging therapy during liso-cel manufacturing. All patients received lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel at 50 x 10⁶ CAR T cells, 100 x 10⁶ CAR T cells, or 150 x 10⁶ CAR T cells.

Response and survival

The median follow-up was 12.0 months. The overall response rate was 73%, and the complete response rate was 53%.

“Remissions were rapid, with a median of 1 month from CAR T-cell infusion, and durable, with a median duration of response that has not been reached and 55% of patients remaining in response at 1 year,” Dr. Abramson said.

The median PFS was 6.8 months overall, not reached for patients who achieved a complete response, 2.8 months for patients with a partial response, and 1.1 months for patients with stable disease or progressive disease.

The median PFS was not reached for patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma, 5.0 months for high-grade B-cell lymphoma, 3.0 months for diffuse large B-cell lymphoma not otherwise specified, and 2.9 months in transformed indolent non-Hodgkin lymphoma.

The median overall survival was 21.1 months overall, not reached for patients who achieved a complete response, 9.0 months for patients who had a partial response, and 5.1 months for patients with stable disease or progressive disease.

Safety

Common treatment-emergent adverse events were neutropenia (63%), anemia (48%), fatigue (44%), nausea (33%), thrombocytopenia (31%), headache (30%), decreased appetite (28%), and diarrhea (26%).

Cytokine release syndrome (CRS) occurred in 42% of patients, and neurologic events occurred in 30%. Grade 3-4 CRS occurred in 2% of patients, and grade 3-4 neurologic events occurred in 10%. There were no cases of grade 5 CRS or neurologic events.

The median time to CRS onset was 5 days, and the median time to onset of neurologic events was 9 days. The median time to resolution of CRS and neurologic events was 5 days and 11 days, respectively.

“The low incidence of severe CRS and neurologic events and their late time of onset support using this product in a large range of patients and in the outpatient setting,” Dr. Abramson said.

There were seven grade 5 treatment-related adverse events, including diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.

This trial is sponsored by Bristol-Myers Squibb. Dr. Abramson reported relationships with Juno Therapeutics and Celgene, now owned by Bristol-Myers Squibb, and a range of other companies.

jensmith@mdedge.com

SOURCE: Abramson JS et al. ASH 2019, Abstract 241.

ORLANDO – Updated results from the TRANSCEND NHL trial include survival data with lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory B-cell lymphomas.

Jennifer Smith/MDedge News

The median progression-free survival (PFS) was 6.8 months, and the median overall survival was 21.1 months. PFS results were best among complete responders and among patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma.

Jeremy S. Abramson, MD, of Massachusetts General Hospital in Boston, presented these results at the annual meeting of the American Society of Hematology.

“TRANSCEND NHL is the largest clinical study to date of CD19-directed CAR T cells in patients with relapsed/refractory aggressive B-cell lymphoma,” Dr. Abramson said.

The phase 1 trial (NCT02631044) includes 269 patients who received liso-cel. They were diagnosed with transformed follicular lymphoma (22%) or other indolent lymphoma (7%), high-grade B-cell lymphoma (13%), primary mediastinal large B-cell lymphoma (6%), grade 3B follicular lymphoma (1%), or diffuse large B-cell lymphoma not otherwise specified (51%).

At baseline, patients had received a median of three prior systemic therapies (range, one to eight). Some patients had received autologous (33%) or allogeneic (3%) transplant. Many patients were chemotherapy refractory (67%) or had never achieved a complete response to prior therapy (44%).

More than half of patients (59%) received bridging therapy during liso-cel manufacturing. All patients received lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel at 50 x 10⁶ CAR T cells, 100 x 10⁶ CAR T cells, or 150 x 10⁶ CAR T cells.

Response and survival

The median follow-up was 12.0 months. The overall response rate was 73%, and the complete response rate was 53%.

“Remissions were rapid, with a median of 1 month from CAR T-cell infusion, and durable, with a median duration of response that has not been reached and 55% of patients remaining in response at 1 year,” Dr. Abramson said.

The median PFS was 6.8 months overall, not reached for patients who achieved a complete response, 2.8 months for patients with a partial response, and 1.1 months for patients with stable disease or progressive disease.

The median PFS was not reached for patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma, 5.0 months for high-grade B-cell lymphoma, 3.0 months for diffuse large B-cell lymphoma not otherwise specified, and 2.9 months in transformed indolent non-Hodgkin lymphoma.

The median overall survival was 21.1 months overall, not reached for patients who achieved a complete response, 9.0 months for patients who had a partial response, and 5.1 months for patients with stable disease or progressive disease.

Safety

Common treatment-emergent adverse events were neutropenia (63%), anemia (48%), fatigue (44%), nausea (33%), thrombocytopenia (31%), headache (30%), decreased appetite (28%), and diarrhea (26%).

Cytokine release syndrome (CRS) occurred in 42% of patients, and neurologic events occurred in 30%. Grade 3-4 CRS occurred in 2% of patients, and grade 3-4 neurologic events occurred in 10%. There were no cases of grade 5 CRS or neurologic events.

The median time to CRS onset was 5 days, and the median time to onset of neurologic events was 9 days. The median time to resolution of CRS and neurologic events was 5 days and 11 days, respectively.

“The low incidence of severe CRS and neurologic events and their late time of onset support using this product in a large range of patients and in the outpatient setting,” Dr. Abramson said.

There were seven grade 5 treatment-related adverse events, including diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.

This trial is sponsored by Bristol-Myers Squibb. Dr. Abramson reported relationships with Juno Therapeutics and Celgene, now owned by Bristol-Myers Squibb, and a range of other companies.

jensmith@mdedge.com

SOURCE: Abramson JS et al. ASH 2019, Abstract 241.

ORLANDO – Updated results from the TRANSCEND NHL trial include survival data with lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory B-cell lymphomas.

Jennifer Smith/MDedge News

The median progression-free survival (PFS) was 6.8 months, and the median overall survival was 21.1 months. PFS results were best among complete responders and among patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma.

Jeremy S. Abramson, MD, of Massachusetts General Hospital in Boston, presented these results at the annual meeting of the American Society of Hematology.

“TRANSCEND NHL is the largest clinical study to date of CD19-directed CAR T cells in patients with relapsed/refractory aggressive B-cell lymphoma,” Dr. Abramson said.

The phase 1 trial (NCT02631044) includes 269 patients who received liso-cel. They were diagnosed with transformed follicular lymphoma (22%) or other indolent lymphoma (7%), high-grade B-cell lymphoma (13%), primary mediastinal large B-cell lymphoma (6%), grade 3B follicular lymphoma (1%), or diffuse large B-cell lymphoma not otherwise specified (51%).

At baseline, patients had received a median of three prior systemic therapies (range, one to eight). Some patients had received autologous (33%) or allogeneic (3%) transplant. Many patients were chemotherapy refractory (67%) or had never achieved a complete response to prior therapy (44%).

More than half of patients (59%) received bridging therapy during liso-cel manufacturing. All patients received lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel at 50 x 10⁶ CAR T cells, 100 x 10⁶ CAR T cells, or 150 x 10⁶ CAR T cells.

Response and survival

The median follow-up was 12.0 months. The overall response rate was 73%, and the complete response rate was 53%.

“Remissions were rapid, with a median of 1 month from CAR T-cell infusion, and durable, with a median duration of response that has not been reached and 55% of patients remaining in response at 1 year,” Dr. Abramson said.

The median PFS was 6.8 months overall, not reached for patients who achieved a complete response, 2.8 months for patients with a partial response, and 1.1 months for patients with stable disease or progressive disease.

The median PFS was not reached for patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma, 5.0 months for high-grade B-cell lymphoma, 3.0 months for diffuse large B-cell lymphoma not otherwise specified, and 2.9 months in transformed indolent non-Hodgkin lymphoma.

The median overall survival was 21.1 months overall, not reached for patients who achieved a complete response, 9.0 months for patients who had a partial response, and 5.1 months for patients with stable disease or progressive disease.

Safety

Common treatment-emergent adverse events were neutropenia (63%), anemia (48%), fatigue (44%), nausea (33%), thrombocytopenia (31%), headache (30%), decreased appetite (28%), and diarrhea (26%).

Cytokine release syndrome (CRS) occurred in 42% of patients, and neurologic events occurred in 30%. Grade 3-4 CRS occurred in 2% of patients, and grade 3-4 neurologic events occurred in 10%. There were no cases of grade 5 CRS or neurologic events.

The median time to CRS onset was 5 days, and the median time to onset of neurologic events was 9 days. The median time to resolution of CRS and neurologic events was 5 days and 11 days, respectively.

“The low incidence of severe CRS and neurologic events and their late time of onset support using this product in a large range of patients and in the outpatient setting,” Dr. Abramson said.

There were seven grade 5 treatment-related adverse events, including diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.

This trial is sponsored by Bristol-Myers Squibb. Dr. Abramson reported relationships with Juno Therapeutics and Celgene, now owned by Bristol-Myers Squibb, and a range of other companies.

jensmith@mdedge.com

SOURCE: Abramson JS et al. ASH 2019, Abstract 241.

ORLANDO – Chimeric antigen receptor (CAR) T-cell therapy has been hailed as a major advance and a game changer, but their cost has redefined the meaning of “expensive.”

However, new “real-world” data now suggests that CAR T-cell therapy may actually be cost effective, as it may lower other expenses related to the illness.

When used in a population of older adults with non-Hodgkin lymphoma, these new data show that CAR T-cell therapy cut related expenditures, compared with health care costs prior to receiving this treatment.

“CAR T therapy was associated with fewer hospitalizations, shorter time in the hospital, fewer ED visits, and lower total health care costs,” said lead study author Karl M. Kilgore, PhD, of Avalere Health in Washington, D.C.

He presented the findings at the 2019 annual meeting of the American Society of Hematology (abstract 793).

CAR T-cell therapies were approved in the United States in 2017. First came tisagenlecleucel (Kymriah, Novartis), for the treatment of pediatric and young adult patients with acute lymphoblastic leukemia, with a price tag of $475,000. Closely following it was axicabtagene ciloleucel (Yescarta, Kite/Gliead), indicated for adult patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant, with a price tag of $373,000.

The formidable price tags sent shock waves through the blood cancers community, which is struggling to incorporate this novel approach because of the remarkable responses that have been seen.

Real-world experience

In the current study, Dr. Kilgore and colleagues evaluated the demographic and clinical characteristics of Medicare patients who received CAR T therapy (axicabtagene ciloleucel or tisagenlecleucel) and then compared health care utilization, costs, and outcomes pre– and post–CAR T therapy.

“The goal of this study was to look at the real use of CAR T-cell therapy and real-world data on the use of these therapies,” said Dr. Kilgore. “And to look at health care utilization.”

Data was obtained from the Centers for Medicare & Medicaid Services 100% Medicare Fee-for-Service Part A and B claims data, and patients were included in the study if they had been diagnosed with lymphoma and received CAR T therapy between Oct. 1, 2017, and Sept. 30, 2018.

A total of 177 patients met all of the inclusion criteria and were included in the analysis.

The average age was 70 years, more than half (58.8%) were male, and they were primarily white (87.6%). Nearly all patients (91.5%) had a primary diagnosis of diffuse large B-cell lymphoma (DLBCL), as well as multiple comorbidities with 74.6% having a Charlson Comorbidity Index score of 3 or less. Fewer than 5% of patients had undergone a previous autologous stem cell transplant, and 51% had one or more comorbidities that would have disqualified them from participating in CAR T clinical trials (for example, renal failure, heart failure, recent history of deep vein thrombosis/pulmonary embolism).

Just over half of participants (52%) had been treated with intravenous chemotherapy in the 6 months prior to receiving CAR T-cell therapy, and 60% received outpatient lymphodepletion.

During their index episode of care for CAR T infusion, the patients spent a median of 16 days (interquartile range, 10) in the hospital during and 45.5% required ICU care after infusion. In the 6-month period prior to CAR T-cell therapy (preindex), 51.2% had been hospitalized at least once, and almost 20% had three or more periods of hospitalization. Of that group, 27.1% were readmitted during the postindex period.

Among patients who required hospitalization, the median length of stay preindex was 7 days and 5 days post index. The number of ED visits was also lower in the post versus preindex (15.8% vs. 29.9%).

“Patients spent 17% less time in the hospital 6 months after CAR T-cell therapy than before,” he said.

While there were no deaths during the postindex period, a small percentage (less than 5%) were admitted to hospice care. It is unclear if any patients received chemotherapy during the 100-day postindex period, which would suggest disease progression. However, the authors note that claims for the period might be lagging behind for some patients.

Dr. Kilgore pointed out that half of the patients had one or more chronic conditions that, in some cases, would have excluded them from clinical trials. “But 73% remain alive at 6 months,” he said. “We have data that goes out to 21 months, and over 50% are still alive at almost 2 years.”

As for cost, the median total health care costs during the preindex period were $51,999 (mean, 58,820; standard deviation, 45,701) and $14,014 post index (mean, 23,738; SD, 29,698). This extrapolates into $9,749 pre- versus $7,121 post index for each patient per month, which is a 27% decrease in expenditures.

Dr. Kilgore explained that the total paid amounts for CAR T from all sources (Medicare and patient) varied significantly, depending on whether patients were treated in a clinical trial and whether the hospital was reimbursed under standard Medicare prospective payment system for inpatient facilities or through the PPS-exempt payment system.

Impressive survival

Commenting on the study, Sarah Rutherford, MD, a hematologist at Weill Cornell Medical College, New York, and New York–Presbyterian, believes that the key takeaway from this study is that the majority of participants – who were older and sicker than many enrolled on CAR T-cell clinical trials – did quite well.

“Diffuse large B-cell lymphoma is a disease that usually causes people to die quickly if they are refractory to multiple lines of therapy, so the 6-month survival of 75% in this patient population is impressive,” she said. “A large proportion of these patients are likely to have died had they not received CAR T-cell therapy.”

Dr. Rutherford noted that the study authors analyzed the costs associated with patients in the pre– and post–CAR T-cell setting, finding that health care costs were lower following CAR T-cell therapy in this Medicare patient subset, compared with costs prior to the therapy.

“I think CAR T-cell use is certainly justified given the lack of efficacious therapies in relapsed and refractory DLBCL patients, and this study indicates that there may be a financial benefit as well, though the actual costs associated with CAR T-cell therapy were not included in the analysis,” she told Medscape Medical News.

Also weighing in on the study, James Essell, MD, from the U.S. Oncology Network, pointed out that CAR T-cell therapy is changing the paradigm of treatment. For example, refractory lymphoma has a life expectancy of about 6 months. “But with newer data we’re seeing about 50% of patients alive at 3 years after CAR T-cell therapy and we’re thinking that will equate into a cure,” he said.

Dr. Essell explained that, in the past, the scenario would be 6 months of chemotherapy, relapse, other chemotherapy, relapse, and then CAR T, but several clinical trials are now looking at giving CAR T at first relapse. “Instead of waiting until they’ve had a transplant, which is going to be about $100,000 at least, they are going to be randomized between autologous transplant and CAR T up front,” he said.

“We are also doing clinical trials through the network for patients who are not candidates for an autologous transplant,” Dr. Essell continued. “They will go straight to CAR-T therapy and that will really increase the cure rate because these are people who weren’t eligible for any curative therapy – and now they are being given a chance.”

Whether CAR T-cell use will expand to broader populations will depend on the results of the randomized trials that are ongoing now, he added.

“That’s our hypotheses right now, but they are being studied in a wide range of hematologic cancers, and in addition, there is a lot of research in solid tumors,” Dr. Essell said. “I don’t think you’d see this mass amount of research and dollars being poured into it if people didn’t think it was going to be a game changer.”

Dr. Kilgore has disclosed research funding from Kite Pharma. Several of the other coauthors have disclosed relationships with industry, which are noted in the abstract. Dr. Essell has disclosed no relevant financial relationships.

A version of this story originally appeared on Medscape.com.

ORLANDO – Chimeric antigen receptor (CAR) T-cell therapy has been hailed as a major advance and a game changer, but their cost has redefined the meaning of “expensive.”

However, new “real-world” data now suggests that CAR T-cell therapy may actually be cost effective, as it may lower other expenses related to the illness.

When used in a population of older adults with non-Hodgkin lymphoma, these new data show that CAR T-cell therapy cut related expenditures, compared with health care costs prior to receiving this treatment.

“CAR T therapy was associated with fewer hospitalizations, shorter time in the hospital, fewer ED visits, and lower total health care costs,” said lead study author Karl M. Kilgore, PhD, of Avalere Health in Washington, D.C.

He presented the findings at the 2019 annual meeting of the American Society of Hematology (abstract 793).

CAR T-cell therapies were approved in the United States in 2017. First came tisagenlecleucel (Kymriah, Novartis), for the treatment of pediatric and young adult patients with acute lymphoblastic leukemia, with a price tag of $475,000. Closely following it was axicabtagene ciloleucel (Yescarta, Kite/Gliead), indicated for adult patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant, with a price tag of $373,000.

The formidable price tags sent shock waves through the blood cancers community, which is struggling to incorporate this novel approach because of the remarkable responses that have been seen.

Real-world experience

In the current study, Dr. Kilgore and colleagues evaluated the demographic and clinical characteristics of Medicare patients who received CAR T therapy (axicabtagene ciloleucel or tisagenlecleucel) and then compared health care utilization, costs, and outcomes pre– and post–CAR T therapy.

“The goal of this study was to look at the real use of CAR T-cell therapy and real-world data on the use of these therapies,” said Dr. Kilgore. “And to look at health care utilization.”

Data was obtained from the Centers for Medicare & Medicaid Services 100% Medicare Fee-for-Service Part A and B claims data, and patients were included in the study if they had been diagnosed with lymphoma and received CAR T therapy between Oct. 1, 2017, and Sept. 30, 2018.

A total of 177 patients met all of the inclusion criteria and were included in the analysis.

The average age was 70 years, more than half (58.8%) were male, and they were primarily white (87.6%). Nearly all patients (91.5%) had a primary diagnosis of diffuse large B-cell lymphoma (DLBCL), as well as multiple comorbidities with 74.6% having a Charlson Comorbidity Index score of 3 or less. Fewer than 5% of patients had undergone a previous autologous stem cell transplant, and 51% had one or more comorbidities that would have disqualified them from participating in CAR T clinical trials (for example, renal failure, heart failure, recent history of deep vein thrombosis/pulmonary embolism).

Just over half of participants (52%) had been treated with intravenous chemotherapy in the 6 months prior to receiving CAR T-cell therapy, and 60% received outpatient lymphodepletion.

During their index episode of care for CAR T infusion, the patients spent a median of 16 days (interquartile range, 10) in the hospital during and 45.5% required ICU care after infusion. In the 6-month period prior to CAR T-cell therapy (preindex), 51.2% had been hospitalized at least once, and almost 20% had three or more periods of hospitalization. Of that group, 27.1% were readmitted during the postindex period.

Among patients who required hospitalization, the median length of stay preindex was 7 days and 5 days post index. The number of ED visits was also lower in the post versus preindex (15.8% vs. 29.9%).

“Patients spent 17% less time in the hospital 6 months after CAR T-cell therapy than before,” he said.

While there were no deaths during the postindex period, a small percentage (less than 5%) were admitted to hospice care. It is unclear if any patients received chemotherapy during the 100-day postindex period, which would suggest disease progression. However, the authors note that claims for the period might be lagging behind for some patients.

Dr. Kilgore pointed out that half of the patients had one or more chronic conditions that, in some cases, would have excluded them from clinical trials. “But 73% remain alive at 6 months,” he said. “We have data that goes out to 21 months, and over 50% are still alive at almost 2 years.”

As for cost, the median total health care costs during the preindex period were $51,999 (mean, 58,820; standard deviation, 45,701) and $14,014 post index (mean, 23,738; SD, 29,698). This extrapolates into $9,749 pre- versus $7,121 post index for each patient per month, which is a 27% decrease in expenditures.

Dr. Kilgore explained that the total paid amounts for CAR T from all sources (Medicare and patient) varied significantly, depending on whether patients were treated in a clinical trial and whether the hospital was reimbursed under standard Medicare prospective payment system for inpatient facilities or through the PPS-exempt payment system.

Impressive survival

Commenting on the study, Sarah Rutherford, MD, a hematologist at Weill Cornell Medical College, New York, and New York–Presbyterian, believes that the key takeaway from this study is that the majority of participants – who were older and sicker than many enrolled on CAR T-cell clinical trials – did quite well.

“Diffuse large B-cell lymphoma is a disease that usually causes people to die quickly if they are refractory to multiple lines of therapy, so the 6-month survival of 75% in this patient population is impressive,” she said. “A large proportion of these patients are likely to have died had they not received CAR T-cell therapy.”

Dr. Rutherford noted that the study authors analyzed the costs associated with patients in the pre– and post–CAR T-cell setting, finding that health care costs were lower following CAR T-cell therapy in this Medicare patient subset, compared with costs prior to the therapy.

“I think CAR T-cell use is certainly justified given the lack of efficacious therapies in relapsed and refractory DLBCL patients, and this study indicates that there may be a financial benefit as well, though the actual costs associated with CAR T-cell therapy were not included in the analysis,” she told Medscape Medical News.

Also weighing in on the study, James Essell, MD, from the U.S. Oncology Network, pointed out that CAR T-cell therapy is changing the paradigm of treatment. For example, refractory lymphoma has a life expectancy of about 6 months. “But with newer data we’re seeing about 50% of patients alive at 3 years after CAR T-cell therapy and we’re thinking that will equate into a cure,” he said.

Dr. Essell explained that, in the past, the scenario would be 6 months of chemotherapy, relapse, other chemotherapy, relapse, and then CAR T, but several clinical trials are now looking at giving CAR T at first relapse. “Instead of waiting until they’ve had a transplant, which is going to be about $100,000 at least, they are going to be randomized between autologous transplant and CAR T up front,” he said.

“We are also doing clinical trials through the network for patients who are not candidates for an autologous transplant,” Dr. Essell continued. “They will go straight to CAR-T therapy and that will really increase the cure rate because these are people who weren’t eligible for any curative therapy – and now they are being given a chance.”

Whether CAR T-cell use will expand to broader populations will depend on the results of the randomized trials that are ongoing now, he added.

“That’s our hypotheses right now, but they are being studied in a wide range of hematologic cancers, and in addition, there is a lot of research in solid tumors,” Dr. Essell said. “I don’t think you’d see this mass amount of research and dollars being poured into it if people didn’t think it was going to be a game changer.”

Dr. Kilgore has disclosed research funding from Kite Pharma. Several of the other coauthors have disclosed relationships with industry, which are noted in the abstract. Dr. Essell has disclosed no relevant financial relationships.

A version of this story originally appeared on Medscape.com.

ORLANDO – Chimeric antigen receptor (CAR) T-cell therapy has been hailed as a major advance and a game changer, but their cost has redefined the meaning of “expensive.”

However, new “real-world” data now suggests that CAR T-cell therapy may actually be cost effective, as it may lower other expenses related to the illness.

When used in a population of older adults with non-Hodgkin lymphoma, these new data show that CAR T-cell therapy cut related expenditures, compared with health care costs prior to receiving this treatment.

“CAR T therapy was associated with fewer hospitalizations, shorter time in the hospital, fewer ED visits, and lower total health care costs,” said lead study author Karl M. Kilgore, PhD, of Avalere Health in Washington, D.C.

He presented the findings at the 2019 annual meeting of the American Society of Hematology (abstract 793).

CAR T-cell therapies were approved in the United States in 2017. First came tisagenlecleucel (Kymriah, Novartis), for the treatment of pediatric and young adult patients with acute lymphoblastic leukemia, with a price tag of $475,000. Closely following it was axicabtagene ciloleucel (Yescarta, Kite/Gliead), indicated for adult patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant, with a price tag of $373,000.

The formidable price tags sent shock waves through the blood cancers community, which is struggling to incorporate this novel approach because of the remarkable responses that have been seen.

Real-world experience

In the current study, Dr. Kilgore and colleagues evaluated the demographic and clinical characteristics of Medicare patients who received CAR T therapy (axicabtagene ciloleucel or tisagenlecleucel) and then compared health care utilization, costs, and outcomes pre– and post–CAR T therapy.

“The goal of this study was to look at the real use of CAR T-cell therapy and real-world data on the use of these therapies,” said Dr. Kilgore. “And to look at health care utilization.”

Data was obtained from the Centers for Medicare & Medicaid Services 100% Medicare Fee-for-Service Part A and B claims data, and patients were included in the study if they had been diagnosed with lymphoma and received CAR T therapy between Oct. 1, 2017, and Sept. 30, 2018.

A total of 177 patients met all of the inclusion criteria and were included in the analysis.

The average age was 70 years, more than half (58.8%) were male, and they were primarily white (87.6%). Nearly all patients (91.5%) had a primary diagnosis of diffuse large B-cell lymphoma (DLBCL), as well as multiple comorbidities with 74.6% having a Charlson Comorbidity Index score of 3 or less. Fewer than 5% of patients had undergone a previous autologous stem cell transplant, and 51% had one or more comorbidities that would have disqualified them from participating in CAR T clinical trials (for example, renal failure, heart failure, recent history of deep vein thrombosis/pulmonary embolism).

Just over half of participants (52%) had been treated with intravenous chemotherapy in the 6 months prior to receiving CAR T-cell therapy, and 60% received outpatient lymphodepletion.

During their index episode of care for CAR T infusion, the patients spent a median of 16 days (interquartile range, 10) in the hospital during and 45.5% required ICU care after infusion. In the 6-month period prior to CAR T-cell therapy (preindex), 51.2% had been hospitalized at least once, and almost 20% had three or more periods of hospitalization. Of that group, 27.1% were readmitted during the postindex period.

Among patients who required hospitalization, the median length of stay preindex was 7 days and 5 days post index. The number of ED visits was also lower in the post versus preindex (15.8% vs. 29.9%).

“Patients spent 17% less time in the hospital 6 months after CAR T-cell therapy than before,” he said.

While there were no deaths during the postindex period, a small percentage (less than 5%) were admitted to hospice care. It is unclear if any patients received chemotherapy during the 100-day postindex period, which would suggest disease progression. However, the authors note that claims for the period might be lagging behind for some patients.

Dr. Kilgore pointed out that half of the patients had one or more chronic conditions that, in some cases, would have excluded them from clinical trials. “But 73% remain alive at 6 months,” he said. “We have data that goes out to 21 months, and over 50% are still alive at almost 2 years.”

As for cost, the median total health care costs during the preindex period were $51,999 (mean, 58,820; standard deviation, 45,701) and $14,014 post index (mean, 23,738; SD, 29,698). This extrapolates into $9,749 pre- versus $7,121 post index for each patient per month, which is a 27% decrease in expenditures.

Dr. Kilgore explained that the total paid amounts for CAR T from all sources (Medicare and patient) varied significantly, depending on whether patients were treated in a clinical trial and whether the hospital was reimbursed under standard Medicare prospective payment system for inpatient facilities or through the PPS-exempt payment system.

Impressive survival

Commenting on the study, Sarah Rutherford, MD, a hematologist at Weill Cornell Medical College, New York, and New York–Presbyterian, believes that the key takeaway from this study is that the majority of participants – who were older and sicker than many enrolled on CAR T-cell clinical trials – did quite well.

“Diffuse large B-cell lymphoma is a disease that usually causes people to die quickly if they are refractory to multiple lines of therapy, so the 6-month survival of 75% in this patient population is impressive,” she said. “A large proportion of these patients are likely to have died had they not received CAR T-cell therapy.”

Dr. Rutherford noted that the study authors analyzed the costs associated with patients in the pre– and post–CAR T-cell setting, finding that health care costs were lower following CAR T-cell therapy in this Medicare patient subset, compared with costs prior to the therapy.

“I think CAR T-cell use is certainly justified given the lack of efficacious therapies in relapsed and refractory DLBCL patients, and this study indicates that there may be a financial benefit as well, though the actual costs associated with CAR T-cell therapy were not included in the analysis,” she told Medscape Medical News.

Also weighing in on the study, James Essell, MD, from the U.S. Oncology Network, pointed out that CAR T-cell therapy is changing the paradigm of treatment. For example, refractory lymphoma has a life expectancy of about 6 months. “But with newer data we’re seeing about 50% of patients alive at 3 years after CAR T-cell therapy and we’re thinking that will equate into a cure,” he said.

Dr. Essell explained that, in the past, the scenario would be 6 months of chemotherapy, relapse, other chemotherapy, relapse, and then CAR T, but several clinical trials are now looking at giving CAR T at first relapse. “Instead of waiting until they’ve had a transplant, which is going to be about $100,000 at least, they are going to be randomized between autologous transplant and CAR T up front,” he said.

“We are also doing clinical trials through the network for patients who are not candidates for an autologous transplant,” Dr. Essell continued. “They will go straight to CAR-T therapy and that will really increase the cure rate because these are people who weren’t eligible for any curative therapy – and now they are being given a chance.”

Whether CAR T-cell use will expand to broader populations will depend on the results of the randomized trials that are ongoing now, he added.

“That’s our hypotheses right now, but they are being studied in a wide range of hematologic cancers, and in addition, there is a lot of research in solid tumors,” Dr. Essell said. “I don’t think you’d see this mass amount of research and dollars being poured into it if people didn’t think it was going to be a game changer.”

Dr. Kilgore has disclosed research funding from Kite Pharma. Several of the other coauthors have disclosed relationships with industry, which are noted in the abstract. Dr. Essell has disclosed no relevant financial relationships.

A version of this story originally appeared on Medscape.com.

ORLANDO – An investigational drug that can achieve the same results as complex cell therapy is creating a buzz at the American Society of Hematology (ASH) meeting.

For the last few years, attention at this meeting has focused on the chimeric antigen receptor (CAR) T cells, mainly “because of their incredible efficacy,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and director of the division of hematology at Johns Hopkins University, Baltimore.

But new results with an off-the-shelf product are “very exciting,” he said, because the drug can be given immediately and appears to achieve similar results.

The new product is mosunetuzumab (Genentech/Roche), a bispecific antibody that targets both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). It works by redirecting T cells to engage and eliminate malignant B cells.

“The concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells – it’s basically an antibody using the patient’s own T cells to do what a CAR T cell would do,” Dr. Brodsky explained.

However, unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab is an off-the-shelf product that can be given to patients immediately (by intravenous infusion).

This is important, commented Dr. Brodsky, because very-poor-prognosis patients can deteriorate rapidly, and some may not survive while the CAR T cells are being made.
 

Clinical trial results

Clinical results come from a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma. These patients had previously been treated with a median of three therapies; in addition, 30 patients (11%) were resistant to or had relapsed after an initial response to CAR T-cell therapy, and 77 patients (29%) had progressed after a stem cell transplant.

“These patients had no available therapy that would be expected to improve survival,” noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

All patients received mosunetuzumab with an initial treatment of eight cycles. Patients who achieved complete remission (CR) stopped therapy, while patients who had a partial response or had stable disease, continued treatment for 17 cycles.

Two-thirds of patients (n = 180; 67%) had aggressive lymphomas, mainly diffuse large B-cell lymphoma (DLBCL; n = 117), while 85 patients (31%) had indolent disease, mainly follicular lymphoma (FL; n = 82). Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.

Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%), and 29 of 67 (43%) had CR.

The complete remissions appear to be long lasting, Dr. Schuster commented. With a median follow-up of 6 months since achieving CR, 17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.

“Some patients have remained in remission without additional therapy for more than a year,” he commented.

In the subgroup of 30 patients who had previously received CAR T-cell therapy, the objective response rate was 38.9%, and CR was achieved in 4 patients (22%). These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy, Dr. Schuster commented.

He also noted that in some of these patients, molecular testing showed that the previously administered CAR T cells increased in number. This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR T-cell treatment.

Dr. Schuster also highlighted the results of repeat treatment with mosunetuzumab. Patients who achieved CR stopped treatment – but if they relapsed, they were treated again, and the responses seen on this repeat treatment were similar to those seen with initial treatment. “This is not seen with the CAR T cells,” he noted.

Adverse events with mosunetuzumab were similar to those seen with CAR T cells, he noted, namely cytokine release syndrome, which was mostly mild and seen in 29% of patients, and neurologic toxicity, which was moderately severe in 4% patients.

Overall, the results show that “mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T,” Dr. Schuster commented in a statement.

Approached for comment, Peter Martin MD, chief of the Lymphoma Program at Weill Cornell Medicine, New York, and New York-Presbyterian, said he was excited to see these new data. “It’s good news any time we find something with the potential to save lives.”

“The more options that we have to offer to people with lymphoma the better,” he told Medscape Medical News. “There will always be scenarios where one approach might be better than another. I think there is a good chance that bispecific antibodies will have fairly broad approval in previously treated DLBCL. In many centers, it may be that bispecific antibodies are used most frequently post–CAR T cells, while in other areas people who aren’t candidates for CAR T cells or can’t receive them for whatever reason [could benefit from this new approach].”

Laurie Sehn, MD, MPH, medical oncologist at the University of British Columbia in Vancouver, Canada, and chair of the Lymphoma Tumour Group, as well as an associate editor of ASH journal Blood, also commented for Medscape Medical News.

She agreed that the new data are exciting and noted that this abstract was chosen for the plenary session. She thought the data in the 30 patients who had already been treated with CAR T cells was interesting. “This is a patient population with no other options that offer durable benefit, and mosunetuzumab clearly has clinical activity, with encouraging responses.”

Dr. Sehn also noted that toxicity seen with the drug was “far less” than has been seen with CAR T cells, and the risk of high-grade cytokine release syndrome and neurological toxicity is “very low.”

There are several other new products that are using this bispecific technology, she noted. One example is Regeneron’s REGN1979, a bispecific antibody targeting CD20 and CD3, which is also being investigated in a clinical trial in relapsed/refractory B-cell non-Hodgkin’s lymphoma, including in patients who were previously treated with CAR T cells (abstract 762).
 

How would it be used clinically?

In response to a question from Medscape Medical News, Dr. Schuster suggested that initial use of mosunetuzumab would be in patients who have already tried CAR T-cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval, he suggested.

Gary Schiller, MD, from UCLA Health, who moderated the press briefing agreed, and said this would be the quickest route to market because it would need only a phase 2 clinical trial in this specific patient population. But this would likely be only the first use for this product, and then it could be expanded to a broader patient population, he added.

Another use would for mosunetuzumab would be to enhance CAR T-cell responses by redirecting the CAR T cells to other antigens without doing any additional gene editing, Dr. Schuster commented. The idea here is to “revive” previously administered CAR T cells that have stopped working, Dr. Schiller added.

This is a chemotherapy-free approach, Dr. Schuster emphasized. “In patients who have not had a lot of chemotherapy, you can see an increase in T cells,” he commented.

Mosunetuzumab “stimulates and invigorates T cells,” and it could be useful as a pretreatment or a bridge to CAR T-cell therapy, he said.

So the product could be used before CAR T-cell therapy, and equally it could be used after CAR T-cell therapy because it could boost responses in both cases.

“Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents,” he added.

Genentech says that mosunetuzumab and another bispecific antibody, CD20-TCB, are being evaluated in a robust clinical development program, both as a monotherapies and in combination with other therapies, in both aggressive and indolent non-Hodgkin’s lymphoma.

Dr. Schuster reported relationships with Celgene, Genentech, Merck, Pharmacyclics, Acerta, AbbVie, Gilead, Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, and Novartis. Coauthors also have multiple disclosures, and several are employees of Genentech and Roche. Dr. Sehn consults with several pharmaceutics companies, including Verastem, Roche/Genentech, Morphosys, Takeda, Janssen, Lundbeck, Amgen, Teva, and AbbVie.
 

A version of this story originally appeared on Medscape.com.

ORLANDO – An investigational drug that can achieve the same results as complex cell therapy is creating a buzz at the American Society of Hematology (ASH) meeting.

For the last few years, attention at this meeting has focused on the chimeric antigen receptor (CAR) T cells, mainly “because of their incredible efficacy,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and director of the division of hematology at Johns Hopkins University, Baltimore.

But new results with an off-the-shelf product are “very exciting,” he said, because the drug can be given immediately and appears to achieve similar results.

The new product is mosunetuzumab (Genentech/Roche), a bispecific antibody that targets both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). It works by redirecting T cells to engage and eliminate malignant B cells.

“The concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells – it’s basically an antibody using the patient’s own T cells to do what a CAR T cell would do,” Dr. Brodsky explained.

However, unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab is an off-the-shelf product that can be given to patients immediately (by intravenous infusion).

This is important, commented Dr. Brodsky, because very-poor-prognosis patients can deteriorate rapidly, and some may not survive while the CAR T cells are being made.
 

Clinical trial results

Clinical results come from a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma. These patients had previously been treated with a median of three therapies; in addition, 30 patients (11%) were resistant to or had relapsed after an initial response to CAR T-cell therapy, and 77 patients (29%) had progressed after a stem cell transplant.

“These patients had no available therapy that would be expected to improve survival,” noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

All patients received mosunetuzumab with an initial treatment of eight cycles. Patients who achieved complete remission (CR) stopped therapy, while patients who had a partial response or had stable disease, continued treatment for 17 cycles.

Two-thirds of patients (n = 180; 67%) had aggressive lymphomas, mainly diffuse large B-cell lymphoma (DLBCL; n = 117), while 85 patients (31%) had indolent disease, mainly follicular lymphoma (FL; n = 82). Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.

Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%), and 29 of 67 (43%) had CR.

The complete remissions appear to be long lasting, Dr. Schuster commented. With a median follow-up of 6 months since achieving CR, 17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.

“Some patients have remained in remission without additional therapy for more than a year,” he commented.

In the subgroup of 30 patients who had previously received CAR T-cell therapy, the objective response rate was 38.9%, and CR was achieved in 4 patients (22%). These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy, Dr. Schuster commented.

He also noted that in some of these patients, molecular testing showed that the previously administered CAR T cells increased in number. This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR T-cell treatment.

Dr. Schuster also highlighted the results of repeat treatment with mosunetuzumab. Patients who achieved CR stopped treatment – but if they relapsed, they were treated again, and the responses seen on this repeat treatment were similar to those seen with initial treatment. “This is not seen with the CAR T cells,” he noted.

Adverse events with mosunetuzumab were similar to those seen with CAR T cells, he noted, namely cytokine release syndrome, which was mostly mild and seen in 29% of patients, and neurologic toxicity, which was moderately severe in 4% patients.

Overall, the results show that “mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T,” Dr. Schuster commented in a statement.

Approached for comment, Peter Martin MD, chief of the Lymphoma Program at Weill Cornell Medicine, New York, and New York-Presbyterian, said he was excited to see these new data. “It’s good news any time we find something with the potential to save lives.”

“The more options that we have to offer to people with lymphoma the better,” he told Medscape Medical News. “There will always be scenarios where one approach might be better than another. I think there is a good chance that bispecific antibodies will have fairly broad approval in previously treated DLBCL. In many centers, it may be that bispecific antibodies are used most frequently post–CAR T cells, while in other areas people who aren’t candidates for CAR T cells or can’t receive them for whatever reason [could benefit from this new approach].”

Laurie Sehn, MD, MPH, medical oncologist at the University of British Columbia in Vancouver, Canada, and chair of the Lymphoma Tumour Group, as well as an associate editor of ASH journal Blood, also commented for Medscape Medical News.

She agreed that the new data are exciting and noted that this abstract was chosen for the plenary session. She thought the data in the 30 patients who had already been treated with CAR T cells was interesting. “This is a patient population with no other options that offer durable benefit, and mosunetuzumab clearly has clinical activity, with encouraging responses.”

Dr. Sehn also noted that toxicity seen with the drug was “far less” than has been seen with CAR T cells, and the risk of high-grade cytokine release syndrome and neurological toxicity is “very low.”

There are several other new products that are using this bispecific technology, she noted. One example is Regeneron’s REGN1979, a bispecific antibody targeting CD20 and CD3, which is also being investigated in a clinical trial in relapsed/refractory B-cell non-Hodgkin’s lymphoma, including in patients who were previously treated with CAR T cells (abstract 762).
 

How would it be used clinically?

In response to a question from Medscape Medical News, Dr. Schuster suggested that initial use of mosunetuzumab would be in patients who have already tried CAR T-cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval, he suggested.

Gary Schiller, MD, from UCLA Health, who moderated the press briefing agreed, and said this would be the quickest route to market because it would need only a phase 2 clinical trial in this specific patient population. But this would likely be only the first use for this product, and then it could be expanded to a broader patient population, he added.

Another use would for mosunetuzumab would be to enhance CAR T-cell responses by redirecting the CAR T cells to other antigens without doing any additional gene editing, Dr. Schuster commented. The idea here is to “revive” previously administered CAR T cells that have stopped working, Dr. Schiller added.

This is a chemotherapy-free approach, Dr. Schuster emphasized. “In patients who have not had a lot of chemotherapy, you can see an increase in T cells,” he commented.

Mosunetuzumab “stimulates and invigorates T cells,” and it could be useful as a pretreatment or a bridge to CAR T-cell therapy, he said.

So the product could be used before CAR T-cell therapy, and equally it could be used after CAR T-cell therapy because it could boost responses in both cases.

“Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents,” he added.

Genentech says that mosunetuzumab and another bispecific antibody, CD20-TCB, are being evaluated in a robust clinical development program, both as a monotherapies and in combination with other therapies, in both aggressive and indolent non-Hodgkin’s lymphoma.

Dr. Schuster reported relationships with Celgene, Genentech, Merck, Pharmacyclics, Acerta, AbbVie, Gilead, Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, and Novartis. Coauthors also have multiple disclosures, and several are employees of Genentech and Roche. Dr. Sehn consults with several pharmaceutics companies, including Verastem, Roche/Genentech, Morphosys, Takeda, Janssen, Lundbeck, Amgen, Teva, and AbbVie.
 

A version of this story originally appeared on Medscape.com.

ORLANDO – An investigational drug that can achieve the same results as complex cell therapy is creating a buzz at the American Society of Hematology (ASH) meeting.

For the last few years, attention at this meeting has focused on the chimeric antigen receptor (CAR) T cells, mainly “because of their incredible efficacy,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and director of the division of hematology at Johns Hopkins University, Baltimore.

But new results with an off-the-shelf product are “very exciting,” he said, because the drug can be given immediately and appears to achieve similar results.

The new product is mosunetuzumab (Genentech/Roche), a bispecific antibody that targets both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). It works by redirecting T cells to engage and eliminate malignant B cells.

“The concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells – it’s basically an antibody using the patient’s own T cells to do what a CAR T cell would do,” Dr. Brodsky explained.

However, unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab is an off-the-shelf product that can be given to patients immediately (by intravenous infusion).

This is important, commented Dr. Brodsky, because very-poor-prognosis patients can deteriorate rapidly, and some may not survive while the CAR T cells are being made.
 

Clinical trial results

Clinical results come from a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma. These patients had previously been treated with a median of three therapies; in addition, 30 patients (11%) were resistant to or had relapsed after an initial response to CAR T-cell therapy, and 77 patients (29%) had progressed after a stem cell transplant.

“These patients had no available therapy that would be expected to improve survival,” noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

All patients received mosunetuzumab with an initial treatment of eight cycles. Patients who achieved complete remission (CR) stopped therapy, while patients who had a partial response or had stable disease, continued treatment for 17 cycles.

Two-thirds of patients (n = 180; 67%) had aggressive lymphomas, mainly diffuse large B-cell lymphoma (DLBCL; n = 117), while 85 patients (31%) had indolent disease, mainly follicular lymphoma (FL; n = 82). Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.

Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%), and 29 of 67 (43%) had CR.

The complete remissions appear to be long lasting, Dr. Schuster commented. With a median follow-up of 6 months since achieving CR, 17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.

“Some patients have remained in remission without additional therapy for more than a year,” he commented.

In the subgroup of 30 patients who had previously received CAR T-cell therapy, the objective response rate was 38.9%, and CR was achieved in 4 patients (22%). These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy, Dr. Schuster commented.

He also noted that in some of these patients, molecular testing showed that the previously administered CAR T cells increased in number. This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR T-cell treatment.

Dr. Schuster also highlighted the results of repeat treatment with mosunetuzumab. Patients who achieved CR stopped treatment – but if they relapsed, they were treated again, and the responses seen on this repeat treatment were similar to those seen with initial treatment. “This is not seen with the CAR T cells,” he noted.

Adverse events with mosunetuzumab were similar to those seen with CAR T cells, he noted, namely cytokine release syndrome, which was mostly mild and seen in 29% of patients, and neurologic toxicity, which was moderately severe in 4% patients.

Overall, the results show that “mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T,” Dr. Schuster commented in a statement.

Approached for comment, Peter Martin MD, chief of the Lymphoma Program at Weill Cornell Medicine, New York, and New York-Presbyterian, said he was excited to see these new data. “It’s good news any time we find something with the potential to save lives.”

“The more options that we have to offer to people with lymphoma the better,” he told Medscape Medical News. “There will always be scenarios where one approach might be better than another. I think there is a good chance that bispecific antibodies will have fairly broad approval in previously treated DLBCL. In many centers, it may be that bispecific antibodies are used most frequently post–CAR T cells, while in other areas people who aren’t candidates for CAR T cells or can’t receive them for whatever reason [could benefit from this new approach].”

Laurie Sehn, MD, MPH, medical oncologist at the University of British Columbia in Vancouver, Canada, and chair of the Lymphoma Tumour Group, as well as an associate editor of ASH journal Blood, also commented for Medscape Medical News.

She agreed that the new data are exciting and noted that this abstract was chosen for the plenary session. She thought the data in the 30 patients who had already been treated with CAR T cells was interesting. “This is a patient population with no other options that offer durable benefit, and mosunetuzumab clearly has clinical activity, with encouraging responses.”

Dr. Sehn also noted that toxicity seen with the drug was “far less” than has been seen with CAR T cells, and the risk of high-grade cytokine release syndrome and neurological toxicity is “very low.”

There are several other new products that are using this bispecific technology, she noted. One example is Regeneron’s REGN1979, a bispecific antibody targeting CD20 and CD3, which is also being investigated in a clinical trial in relapsed/refractory B-cell non-Hodgkin’s lymphoma, including in patients who were previously treated with CAR T cells (abstract 762).
 

How would it be used clinically?

In response to a question from Medscape Medical News, Dr. Schuster suggested that initial use of mosunetuzumab would be in patients who have already tried CAR T-cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval, he suggested.

Gary Schiller, MD, from UCLA Health, who moderated the press briefing agreed, and said this would be the quickest route to market because it would need only a phase 2 clinical trial in this specific patient population. But this would likely be only the first use for this product, and then it could be expanded to a broader patient population, he added.

Another use would for mosunetuzumab would be to enhance CAR T-cell responses by redirecting the CAR T cells to other antigens without doing any additional gene editing, Dr. Schuster commented. The idea here is to “revive” previously administered CAR T cells that have stopped working, Dr. Schiller added.

This is a chemotherapy-free approach, Dr. Schuster emphasized. “In patients who have not had a lot of chemotherapy, you can see an increase in T cells,” he commented.

Mosunetuzumab “stimulates and invigorates T cells,” and it could be useful as a pretreatment or a bridge to CAR T-cell therapy, he said.

So the product could be used before CAR T-cell therapy, and equally it could be used after CAR T-cell therapy because it could boost responses in both cases.

“Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents,” he added.

Genentech says that mosunetuzumab and another bispecific antibody, CD20-TCB, are being evaluated in a robust clinical development program, both as a monotherapies and in combination with other therapies, in both aggressive and indolent non-Hodgkin’s lymphoma.

Dr. Schuster reported relationships with Celgene, Genentech, Merck, Pharmacyclics, Acerta, AbbVie, Gilead, Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, and Novartis. Coauthors also have multiple disclosures, and several are employees of Genentech and Roche. Dr. Sehn consults with several pharmaceutics companies, including Verastem, Roche/Genentech, Morphosys, Takeda, Janssen, Lundbeck, Amgen, Teva, and AbbVie.
 

A version of this story originally appeared on Medscape.com.

ORLANDO – A cellular therapy called FT596 is active against B-cell malignancies and, when combined with rituximab, can be more effective than traditional chimeric antigen receptor (CAR) T cells, preclinical research findings suggest.

Jennifer Smith/MDedge News

FT596 is a universal, anti-CD19 CAR natural killer (NK) cell therapy derived from a master induced pluripotent stem cell (iPSC) line.

FT596 reduced tumor growth in mouse models of leukemia and lymphoma. When combined with rituximab, FT596 was able to overcome CD19 antigen escape.

Jode P. Goodridge, PhD, of Fate Therapeutics in San Diego, presented these results at the annual meeting of the American Society of Hematology.

Dr. Goodridge explained that FT596 begins with a source material, such as a fibroblast, that is reprogrammed into an iPSC progenitor cell. That cell is sorted and expanded into a renewable, homogeneous, pluripotent master iPSC line. The iPSCs are differentiated into CD34 cells, which are differentiated into NK cells. The iPSC-derived NK cells are then modified with the following:

• An anti-CD19 CAR that is optimized for NK-cell biology and contains an NKG2D transmembrane domain, a 2B4 costimulatory domain, and a CD3-zeta signaling domain.
• An interleukin-15 receptor fusion that promotes cell survival and reduces the need for cytokine support.
• A high-affinity 158V, noncleavable CD16 Fc receptor that enhances antibody-dependent cellular cytotoxicity when FT596 is combined with a monoclonal antibody such as rituximab.

Dr. Goodridge presented results with FT596, both alone and in combination with rituximab, in vitro and in vivo.

When compared with no treatment, three doses of FT596 monotherapy reduced tumor growth in a mouse model of leukemia (Nalm6). FT596 plus rituximab reduced tumor growth in a mouse model of lymphoma (Raji), when compared with no treatment or rituximab alone.

Three doses of FT596 proved more effective than a single dose of CD19 CAR T-cell therapy in a mouse model of lymphoma (Raji). FT596 both reduced tumor growth and prolonged survival in the mice.

Lastly, in vitro experiments in Raji cells showed that FT596 plus rituximab can produce deeper responses than primary CAR-T cells, and the combination can prevent antigen escape.

Dr. Goodridge said these results support the phase 1 study of FT596, given as monotherapy or in combination with rituximab or obinutuzumab, in patients with relapsed/refractory B-cell lymphomas or chronic lymphocytic leukemia.

Dr. Goodridge is employed by Fate Therapeutics, the company developing FT596.

jensmith@mdedge.com

SOURCE: Goodridge JP et al. ASH 2019. Abstract 301.

ORLANDO – A cellular therapy called FT596 is active against B-cell malignancies and, when combined with rituximab, can be more effective than traditional chimeric antigen receptor (CAR) T cells, preclinical research findings suggest.

Jennifer Smith/MDedge News

FT596 is a universal, anti-CD19 CAR natural killer (NK) cell therapy derived from a master induced pluripotent stem cell (iPSC) line.

FT596 reduced tumor growth in mouse models of leukemia and lymphoma. When combined with rituximab, FT596 was able to overcome CD19 antigen escape.

Jode P. Goodridge, PhD, of Fate Therapeutics in San Diego, presented these results at the annual meeting of the American Society of Hematology.

Dr. Goodridge explained that FT596 begins with a source material, such as a fibroblast, that is reprogrammed into an iPSC progenitor cell. That cell is sorted and expanded into a renewable, homogeneous, pluripotent master iPSC line. The iPSCs are differentiated into CD34 cells, which are differentiated into NK cells. The iPSC-derived NK cells are then modified with the following:

• An anti-CD19 CAR that is optimized for NK-cell biology and contains an NKG2D transmembrane domain, a 2B4 costimulatory domain, and a CD3-zeta signaling domain.
• An interleukin-15 receptor fusion that promotes cell survival and reduces the need for cytokine support.
• A high-affinity 158V, noncleavable CD16 Fc receptor that enhances antibody-dependent cellular cytotoxicity when FT596 is combined with a monoclonal antibody such as rituximab.

Dr. Goodridge presented results with FT596, both alone and in combination with rituximab, in vitro and in vivo.

When compared with no treatment, three doses of FT596 monotherapy reduced tumor growth in a mouse model of leukemia (Nalm6). FT596 plus rituximab reduced tumor growth in a mouse model of lymphoma (Raji), when compared with no treatment or rituximab alone.

Three doses of FT596 proved more effective than a single dose of CD19 CAR T-cell therapy in a mouse model of lymphoma (Raji). FT596 both reduced tumor growth and prolonged survival in the mice.

Lastly, in vitro experiments in Raji cells showed that FT596 plus rituximab can produce deeper responses than primary CAR-T cells, and the combination can prevent antigen escape.

Dr. Goodridge said these results support the phase 1 study of FT596, given as monotherapy or in combination with rituximab or obinutuzumab, in patients with relapsed/refractory B-cell lymphomas or chronic lymphocytic leukemia.

Dr. Goodridge is employed by Fate Therapeutics, the company developing FT596.

jensmith@mdedge.com

SOURCE: Goodridge JP et al. ASH 2019. Abstract 301.

ORLANDO – A cellular therapy called FT596 is active against B-cell malignancies and, when combined with rituximab, can be more effective than traditional chimeric antigen receptor (CAR) T cells, preclinical research findings suggest.

Jennifer Smith/MDedge News

FT596 is a universal, anti-CD19 CAR natural killer (NK) cell therapy derived from a master induced pluripotent stem cell (iPSC) line.

FT596 reduced tumor growth in mouse models of leukemia and lymphoma. When combined with rituximab, FT596 was able to overcome CD19 antigen escape.

Jode P. Goodridge, PhD, of Fate Therapeutics in San Diego, presented these results at the annual meeting of the American Society of Hematology.

Dr. Goodridge explained that FT596 begins with a source material, such as a fibroblast, that is reprogrammed into an iPSC progenitor cell. That cell is sorted and expanded into a renewable, homogeneous, pluripotent master iPSC line. The iPSCs are differentiated into CD34 cells, which are differentiated into NK cells. The iPSC-derived NK cells are then modified with the following:

• An anti-CD19 CAR that is optimized for NK-cell biology and contains an NKG2D transmembrane domain, a 2B4 costimulatory domain, and a CD3-zeta signaling domain.
• An interleukin-15 receptor fusion that promotes cell survival and reduces the need for cytokine support.
• A high-affinity 158V, noncleavable CD16 Fc receptor that enhances antibody-dependent cellular cytotoxicity when FT596 is combined with a monoclonal antibody such as rituximab.

Dr. Goodridge presented results with FT596, both alone and in combination with rituximab, in vitro and in vivo.

When compared with no treatment, three doses of FT596 monotherapy reduced tumor growth in a mouse model of leukemia (Nalm6). FT596 plus rituximab reduced tumor growth in a mouse model of lymphoma (Raji), when compared with no treatment or rituximab alone.

Three doses of FT596 proved more effective than a single dose of CD19 CAR T-cell therapy in a mouse model of lymphoma (Raji). FT596 both reduced tumor growth and prolonged survival in the mice.

Lastly, in vitro experiments in Raji cells showed that FT596 plus rituximab can produce deeper responses than primary CAR-T cells, and the combination can prevent antigen escape.

Dr. Goodridge said these results support the phase 1 study of FT596, given as monotherapy or in combination with rituximab or obinutuzumab, in patients with relapsed/refractory B-cell lymphomas or chronic lymphocytic leukemia.

Dr. Goodridge is employed by Fate Therapeutics, the company developing FT596.

jensmith@mdedge.com

SOURCE: Goodridge JP et al. ASH 2019. Abstract 301.

ORLANDO – A dual-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated a high overall response rate, a long response duration, and manageable safety in patients with relapsed or refractory multiple myeloma, according to an investigator in a phase 1 study.

Benjamin Pena/Medscape

The overall response rate exceeded 90%, and about three-quarters of patients remained progression-free at 9 months after treatment with the CAR T-cell therapy, which targets both B-cell maturation antigen (BCMA) and CD38, the study investigator reported.

Grade 3 or greater cytokine release syndrome (CRS) occurred in about one-quarter of the patients, and no neurotoxicity was observed, according to investigator Yu Hu, MD, of Tongji Medical College in Hubei, China.

“These initial data provide strong evidence to support the further development of a dual-targeted CAR T-cell therapy for hard to treat multiple myeloma,” Dr. Hu said in a press conference.

Short-term relapse has been a “major challenge” with current CAR T-cell therapies currently under investigation for myeloma, most of which target BCMA, according to Dr. Hu.

He said the bispecific CAR T-cell therapy under investigation, known as BM38, was designed to target antigen loss and increase persistence of effector cells. According to the investigator, this was the first study to focus on an anti-BCMA and CD38 dual-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma.

Gary J. Schiller, MD, of UCLA Health, who moderated the press conference, said that while dual-targeting is a potentially “attractive” approach in these hard-to-treat patients, further follow-up is needed to see duration of response and to see if antigen escape re-emerges.

“Cellular therapy is costly, in terms of toxicity as well as financial costs, so you would like to see what the durability of responses is before engaging in that as a late-stage therapy, not to mention moving it up front,” Dr. Schiller said in an interview.

The median progression-free survival (PFS) duration had not been reached at the time of this report, though the 9-month PFS rate was 78.87%, according to the data presented by Dr. Hu.

SOURCE: Li C et al. ASH 2019. Abstract 930.

ORLANDO – A dual-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated a high overall response rate, a long response duration, and manageable safety in patients with relapsed or refractory multiple myeloma, according to an investigator in a phase 1 study.

Benjamin Pena/Medscape

The overall response rate exceeded 90%, and about three-quarters of patients remained progression-free at 9 months after treatment with the CAR T-cell therapy, which targets both B-cell maturation antigen (BCMA) and CD38, the study investigator reported.

Grade 3 or greater cytokine release syndrome (CRS) occurred in about one-quarter of the patients, and no neurotoxicity was observed, according to investigator Yu Hu, MD, of Tongji Medical College in Hubei, China.

“These initial data provide strong evidence to support the further development of a dual-targeted CAR T-cell therapy for hard to treat multiple myeloma,” Dr. Hu said in a press conference.

Short-term relapse has been a “major challenge” with current CAR T-cell therapies currently under investigation for myeloma, most of which target BCMA, according to Dr. Hu.

He said the bispecific CAR T-cell therapy under investigation, known as BM38, was designed to target antigen loss and increase persistence of effector cells. According to the investigator, this was the first study to focus on an anti-BCMA and CD38 dual-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma.

Gary J. Schiller, MD, of UCLA Health, who moderated the press conference, said that while dual-targeting is a potentially “attractive” approach in these hard-to-treat patients, further follow-up is needed to see duration of response and to see if antigen escape re-emerges.

“Cellular therapy is costly, in terms of toxicity as well as financial costs, so you would like to see what the durability of responses is before engaging in that as a late-stage therapy, not to mention moving it up front,” Dr. Schiller said in an interview.

The median progression-free survival (PFS) duration had not been reached at the time of this report, though the 9-month PFS rate was 78.87%, according to the data presented by Dr. Hu.

SOURCE: Li C et al. ASH 2019. Abstract 930.

ORLANDO – A dual-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated a high overall response rate, a long response duration, and manageable safety in patients with relapsed or refractory multiple myeloma, according to an investigator in a phase 1 study.

Benjamin Pena/Medscape

The overall response rate exceeded 90%, and about three-quarters of patients remained progression-free at 9 months after treatment with the CAR T-cell therapy, which targets both B-cell maturation antigen (BCMA) and CD38, the study investigator reported.

Grade 3 or greater cytokine release syndrome (CRS) occurred in about one-quarter of the patients, and no neurotoxicity was observed, according to investigator Yu Hu, MD, of Tongji Medical College in Hubei, China.

“These initial data provide strong evidence to support the further development of a dual-targeted CAR T-cell therapy for hard to treat multiple myeloma,” Dr. Hu said in a press conference.

Short-term relapse has been a “major challenge” with current CAR T-cell therapies currently under investigation for myeloma, most of which target BCMA, according to Dr. Hu.

He said the bispecific CAR T-cell therapy under investigation, known as BM38, was designed to target antigen loss and increase persistence of effector cells. According to the investigator, this was the first study to focus on an anti-BCMA and CD38 dual-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma.

Gary J. Schiller, MD, of UCLA Health, who moderated the press conference, said that while dual-targeting is a potentially “attractive” approach in these hard-to-treat patients, further follow-up is needed to see duration of response and to see if antigen escape re-emerges.

“Cellular therapy is costly, in terms of toxicity as well as financial costs, so you would like to see what the durability of responses is before engaging in that as a late-stage therapy, not to mention moving it up front,” Dr. Schiller said in an interview.

The median progression-free survival (PFS) duration had not been reached at the time of this report, though the 9-month PFS rate was 78.87%, according to the data presented by Dr. Hu.

SOURCE: Li C et al. ASH 2019. Abstract 930.

ORLANDO – A novel chimeric antigen receptor T (CAR T) cell construct is associated with deep clinical responses in patients with multiple myeloma for whom prior lines of therapy – some numbering in the double digits – have failed.

Nephron/Wikimedia Commons

Among 29 patients with multiple myeloma enrolled in a phase 1b/2 trial of JNJ-4528, the overall response rate (ORR) at 6 months median follow-up was 100%, including 69% complete responses, with 27 patients remaining free of disease progression at a median of 6 months, reported Deepu Madduri, MD, of Icahn School of Medicine at Mount Sinai, New York.

Benjamin Pena/Medscape

“These are very heavily pretreated patients, and so getting early and deep responses is quite amazing,” she said at a briefing prior to presentation of the data at the annual meeting of the American Society of Hematology.

JNJ-4528 is a second-generation CAR T containing two single-domain antibodies targeted against B-cell maturation protein (BCMA). As previously reported, an identical CAR T cell construct showed a high overall response with manageable toxicities in 74 patients with relapsed/refractory multiple myeloma. JNJ-4528 was granted a breakthrough therapy designation for relapsed/refractory multiple myeloma by the Food and Drug Administration on Dec. 6, 2019, and a priority medicines (PRIME) designation by the European Medicines Agency in April 2019.

BCMA was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells. Several research groups are currently investigating CAR T cells or monoclonal antibodies targeted to BCMA. The product closest to receiving FDA approval is likely BB2121.

SOURCE: Madduri D et al. ASH 2019. Abstract 577.

ORLANDO – A novel chimeric antigen receptor T (CAR T) cell construct is associated with deep clinical responses in patients with multiple myeloma for whom prior lines of therapy – some numbering in the double digits – have failed.

Nephron/Wikimedia Commons

Among 29 patients with multiple myeloma enrolled in a phase 1b/2 trial of JNJ-4528, the overall response rate (ORR) at 6 months median follow-up was 100%, including 69% complete responses, with 27 patients remaining free of disease progression at a median of 6 months, reported Deepu Madduri, MD, of Icahn School of Medicine at Mount Sinai, New York.

Benjamin Pena/Medscape

“These are very heavily pretreated patients, and so getting early and deep responses is quite amazing,” she said at a briefing prior to presentation of the data at the annual meeting of the American Society of Hematology.

JNJ-4528 is a second-generation CAR T containing two single-domain antibodies targeted against B-cell maturation protein (BCMA). As previously reported, an identical CAR T cell construct showed a high overall response with manageable toxicities in 74 patients with relapsed/refractory multiple myeloma. JNJ-4528 was granted a breakthrough therapy designation for relapsed/refractory multiple myeloma by the Food and Drug Administration on Dec. 6, 2019, and a priority medicines (PRIME) designation by the European Medicines Agency in April 2019.

BCMA was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells. Several research groups are currently investigating CAR T cells or monoclonal antibodies targeted to BCMA. The product closest to receiving FDA approval is likely BB2121.

SOURCE: Madduri D et al. ASH 2019. Abstract 577.

ORLANDO – A novel chimeric antigen receptor T (CAR T) cell construct is associated with deep clinical responses in patients with multiple myeloma for whom prior lines of therapy – some numbering in the double digits – have failed.

Nephron/Wikimedia Commons

Among 29 patients with multiple myeloma enrolled in a phase 1b/2 trial of JNJ-4528, the overall response rate (ORR) at 6 months median follow-up was 100%, including 69% complete responses, with 27 patients remaining free of disease progression at a median of 6 months, reported Deepu Madduri, MD, of Icahn School of Medicine at Mount Sinai, New York.

Benjamin Pena/Medscape

“These are very heavily pretreated patients, and so getting early and deep responses is quite amazing,” she said at a briefing prior to presentation of the data at the annual meeting of the American Society of Hematology.

JNJ-4528 is a second-generation CAR T containing two single-domain antibodies targeted against B-cell maturation protein (BCMA). As previously reported, an identical CAR T cell construct showed a high overall response with manageable toxicities in 74 patients with relapsed/refractory multiple myeloma. JNJ-4528 was granted a breakthrough therapy designation for relapsed/refractory multiple myeloma by the Food and Drug Administration on Dec. 6, 2019, and a priority medicines (PRIME) designation by the European Medicines Agency in April 2019.

BCMA was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells. Several research groups are currently investigating CAR T cells or monoclonal antibodies targeted to BCMA. The product closest to receiving FDA approval is likely BB2121.

SOURCE: Madduri D et al. ASH 2019. Abstract 577.