Neil Osterweil

SAN DIEGO – A recurrent mutation in BCL2, the therapeutic target of venetoclax (Venclexta), appears to be a major contributor to drug resistance in patients with chronic lymphocytic leukemia (CLL), investigators reported.

The mutation has been detected in some patients with CLL up to 2 years before resistance to venetoclax actually develops, said lead author Piers Blombery, MBBS, from the Peter MacCallum Cancer Center in Melbourne.

“We have identified the first acquired BCL2 mutation developed in patients clinically treated with venetoclax,” he said in a late-breaking oral abstract session at the annual meeting of the American Society of Hematology.

The mutation, which the investigators have labeled BCL2 Gly101Val, “is a recurrent and frequent mediator of resistance and may be detected years before clinical relapse occurs,” he added.

The paper was published online in Cancer Discovery (2018 Dec 4. doi: 10.1158/2159-8290.CD-18-1119) to coincide with the presentation at ASH.

Despite the demonstrated efficacy of venetoclax as continuous therapy in patients with relapsed or refractory CLL, the majority of patients experience disease progression, prompting the investigators to explore molecular mechanisms of secondary resistance.

To do this, they analyzed paired samples from 15 patients with CLL, enrolled in clinical trials of venetoclax, collected both before the start of venetoclax therapy and at the time of disease progression.

In seven of the patients, they identified a novel mutation that showed up at the time of progression, but was absent from the pre-venetoclax samples. The mutation first became detectable from about 19 to 42 months after the start of therapy and preceded clinical progression by as much as 25 months, the investigators found.

They pinned the mutation down to the BH3-binding groove on BCL2, the same molecular site targeted by venetoclax. They found that the mutation was not present in samples from 96 patients with venetoclax-naive CLL nor in any other B-cell malignancies. Searches for references to the mutation in both a cancer database (COSMIC) and a population database (gnomAD) came up empty.

In other experiments, they determined that cell lines overexpressing BCL2 Gly101Val are resistant to venetoclax, and that in the presence of venetoclax in vitro, BCL2 Gly101Val-expressing cells have a growth advantage, compared with wild type cells.

Additionally, they showed that the mutation results in impaired venetoclax binding in vitro.

“BCL2 Gly101Val is observed subclonally, implicating multiple mechanisms of venetoclax resistance in the same patient,” Dr. Blombery said.

In an interview, Dr. Blombery said that the identification of the resistance mutation is a strong rationale for using combination therapy to treat patients with relapsed or refractory CLL to help prevent or attenuate selection pressures that lead to resistance.

The investigators were supported by the Wilson Center for Lymphoma Genomics, Snowdome Foundation, National Health Medical Research Council, Leukemia and Lymphoma Society, Leukemia Foundation, Cancer Council of Victoria, and Australian Cancer Research Foundation. Dr. Blombery reported having no relevant disclosures.

SOURCE: Blombery P et al. ASH 2018, Abstract LBA-7.

SAN DIEGO – A recurrent mutation in BCL2, the therapeutic target of venetoclax (Venclexta), appears to be a major contributor to drug resistance in patients with chronic lymphocytic leukemia (CLL), investigators reported.

The mutation has been detected in some patients with CLL up to 2 years before resistance to venetoclax actually develops, said lead author Piers Blombery, MBBS, from the Peter MacCallum Cancer Center in Melbourne.

“We have identified the first acquired BCL2 mutation developed in patients clinically treated with venetoclax,” he said in a late-breaking oral abstract session at the annual meeting of the American Society of Hematology.

The mutation, which the investigators have labeled BCL2 Gly101Val, “is a recurrent and frequent mediator of resistance and may be detected years before clinical relapse occurs,” he added.

The paper was published online in Cancer Discovery (2018 Dec 4. doi: 10.1158/2159-8290.CD-18-1119) to coincide with the presentation at ASH.

Despite the demonstrated efficacy of venetoclax as continuous therapy in patients with relapsed or refractory CLL, the majority of patients experience disease progression, prompting the investigators to explore molecular mechanisms of secondary resistance.

To do this, they analyzed paired samples from 15 patients with CLL, enrolled in clinical trials of venetoclax, collected both before the start of venetoclax therapy and at the time of disease progression.

In seven of the patients, they identified a novel mutation that showed up at the time of progression, but was absent from the pre-venetoclax samples. The mutation first became detectable from about 19 to 42 months after the start of therapy and preceded clinical progression by as much as 25 months, the investigators found.

They pinned the mutation down to the BH3-binding groove on BCL2, the same molecular site targeted by venetoclax. They found that the mutation was not present in samples from 96 patients with venetoclax-naive CLL nor in any other B-cell malignancies. Searches for references to the mutation in both a cancer database (COSMIC) and a population database (gnomAD) came up empty.

In other experiments, they determined that cell lines overexpressing BCL2 Gly101Val are resistant to venetoclax, and that in the presence of venetoclax in vitro, BCL2 Gly101Val-expressing cells have a growth advantage, compared with wild type cells.

Additionally, they showed that the mutation results in impaired venetoclax binding in vitro.

“BCL2 Gly101Val is observed subclonally, implicating multiple mechanisms of venetoclax resistance in the same patient,” Dr. Blombery said.

In an interview, Dr. Blombery said that the identification of the resistance mutation is a strong rationale for using combination therapy to treat patients with relapsed or refractory CLL to help prevent or attenuate selection pressures that lead to resistance.

The investigators were supported by the Wilson Center for Lymphoma Genomics, Snowdome Foundation, National Health Medical Research Council, Leukemia and Lymphoma Society, Leukemia Foundation, Cancer Council of Victoria, and Australian Cancer Research Foundation. Dr. Blombery reported having no relevant disclosures.

SOURCE: Blombery P et al. ASH 2018, Abstract LBA-7.

SAN DIEGO – A recurrent mutation in BCL2, the therapeutic target of venetoclax (Venclexta), appears to be a major contributor to drug resistance in patients with chronic lymphocytic leukemia (CLL), investigators reported.

The mutation has been detected in some patients with CLL up to 2 years before resistance to venetoclax actually develops, said lead author Piers Blombery, MBBS, from the Peter MacCallum Cancer Center in Melbourne.

“We have identified the first acquired BCL2 mutation developed in patients clinically treated with venetoclax,” he said in a late-breaking oral abstract session at the annual meeting of the American Society of Hematology.

The mutation, which the investigators have labeled BCL2 Gly101Val, “is a recurrent and frequent mediator of resistance and may be detected years before clinical relapse occurs,” he added.

The paper was published online in Cancer Discovery (2018 Dec 4. doi: 10.1158/2159-8290.CD-18-1119) to coincide with the presentation at ASH.

Despite the demonstrated efficacy of venetoclax as continuous therapy in patients with relapsed or refractory CLL, the majority of patients experience disease progression, prompting the investigators to explore molecular mechanisms of secondary resistance.

To do this, they analyzed paired samples from 15 patients with CLL, enrolled in clinical trials of venetoclax, collected both before the start of venetoclax therapy and at the time of disease progression.

In seven of the patients, they identified a novel mutation that showed up at the time of progression, but was absent from the pre-venetoclax samples. The mutation first became detectable from about 19 to 42 months after the start of therapy and preceded clinical progression by as much as 25 months, the investigators found.

They pinned the mutation down to the BH3-binding groove on BCL2, the same molecular site targeted by venetoclax. They found that the mutation was not present in samples from 96 patients with venetoclax-naive CLL nor in any other B-cell malignancies. Searches for references to the mutation in both a cancer database (COSMIC) and a population database (gnomAD) came up empty.

In other experiments, they determined that cell lines overexpressing BCL2 Gly101Val are resistant to venetoclax, and that in the presence of venetoclax in vitro, BCL2 Gly101Val-expressing cells have a growth advantage, compared with wild type cells.

Additionally, they showed that the mutation results in impaired venetoclax binding in vitro.

“BCL2 Gly101Val is observed subclonally, implicating multiple mechanisms of venetoclax resistance in the same patient,” Dr. Blombery said.

In an interview, Dr. Blombery said that the identification of the resistance mutation is a strong rationale for using combination therapy to treat patients with relapsed or refractory CLL to help prevent or attenuate selection pressures that lead to resistance.

The investigators were supported by the Wilson Center for Lymphoma Genomics, Snowdome Foundation, National Health Medical Research Council, Leukemia and Lymphoma Society, Leukemia Foundation, Cancer Council of Victoria, and Australian Cancer Research Foundation. Dr. Blombery reported having no relevant disclosures.

SOURCE: Blombery P et al. ASH 2018, Abstract LBA-7.

SAN ANTONIO – Swapping trastuzumab out for the drug-antibody conjugate trastuzumab emtansine (T-DM1; Kadcyla) as adjuvant therapy resulted in a halving in the risk of invasive disease or death in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy, including trastuzumab.

For the primary endpoint in the KATHERINE trial of invasive disease-free survival – defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – T-DM1 was associated with a hazard ratio of 0.50 (P less than .001).

The 3-year invasive disease-free survival rate for 743 patients treated with T-DMI 1 was 88.3%, compared with 77% for 743 patients treated with trastuzumab, reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond, at the San Antonio Breast Cancer Symposium.

In a video interview, Dr. Geyer discussed results of KATHERINE, which suggest that T-DM1 should be considered as a new standard of care in this patient population.

Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene.

SAN ANTONIO – Swapping trastuzumab out for the drug-antibody conjugate trastuzumab emtansine (T-DM1; Kadcyla) as adjuvant therapy resulted in a halving in the risk of invasive disease or death in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy, including trastuzumab.

For the primary endpoint in the KATHERINE trial of invasive disease-free survival – defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – T-DM1 was associated with a hazard ratio of 0.50 (P less than .001).

The 3-year invasive disease-free survival rate for 743 patients treated with T-DMI 1 was 88.3%, compared with 77% for 743 patients treated with trastuzumab, reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond, at the San Antonio Breast Cancer Symposium.

In a video interview, Dr. Geyer discussed results of KATHERINE, which suggest that T-DM1 should be considered as a new standard of care in this patient population.

Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene.

SAN ANTONIO – Swapping trastuzumab out for the drug-antibody conjugate trastuzumab emtansine (T-DM1; Kadcyla) as adjuvant therapy resulted in a halving in the risk of invasive disease or death in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy, including trastuzumab.

For the primary endpoint in the KATHERINE trial of invasive disease-free survival – defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – T-DM1 was associated with a hazard ratio of 0.50 (P less than .001).

The 3-year invasive disease-free survival rate for 743 patients treated with T-DMI 1 was 88.3%, compared with 77% for 743 patients treated with trastuzumab, reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond, at the San Antonio Breast Cancer Symposium.

In a video interview, Dr. Geyer discussed results of KATHERINE, which suggest that T-DM1 should be considered as a new standard of care in this patient population.

Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene.

SAN DIEGO – In patients with newly diagnosed acute myeloid leukemia (AML) bearing IDH1 or IDH2 mutations, combinations of either ivosidenib (Tibsovo, for IDH1) or enasidenib (Idhifa, for IDH2) with standard induction and consolidation regimens are safe and well tolerated and are associated with encouraging remission rates, results of a phase 1 trial indicate.

In the open-label, phase 1 trial, ivosidenib plus chemotherapy was associated with elimination of minimal residual disease (MRD) by flow cytometry in 88% of treated patients and with IDH1-mutation clearance in 41% of patients.

Enasidenib plus chemotherapy was associated with elimination of MRD in 45% of patients and with IDH2-mutation clearance in 25% of patients, said Eytan M. Stein, MD, from Memorial Sloan Kettering Cancer Center in New York.

“The overall survival rates are robust, with greater than 75% 1-year survival in both ivosidenib- and enasidenib-treated patients,” he said at the annual meeting of the American Society of Hematology.

Both ivosidenib and enasidenib are approved in the United States for treatment of patients with relapsed or refractory AML bearing either IDH1 or IDH2 mutations, respectively. In this trial, the investigators explored the therapeutic potential of the IDH inhibitors in patients with previously untreated disease.

Dr. Stein and his colleagues investigated combining each of the agents with standard induction therapy with either daunorubicin 60 mg/m² per day or idarubicin 12 mg/m² per day for 3 days, plus cytarabine 200 mg/m² per day for 7 days. Patients with IDH1 mutations received ivosidenib 500 mg once daily, and those with IDH2 mutations received enasidenib 100 mg once daily.

After induction, patients with a complete remission (CR), CR with incomplete recovery of hematologic counts (CRi), or CR with incomplete recovery of platelets (CRp) could receive up to four cycles of consolidation therapy while continuing the IDH inhibitor. Patients who completed consolidation or were ineligible for consolidation could continue on maintenance therapy with their assigned drug until the end of the study.

The drugs were discontinued in patients who went on to hematopoietic stem cell transplant.

The most frequent co-occurring baseline mutations were DNMT3A, NPM1, and NRAS for patients with IDH1 mutations, and DNMT3A, SRSF2, and ASXL1 for patients with IDH2 mutations.

A total of 60 patients were assigned to ivosidenib and chemotherapy and 93 were assigned to enasidenib/chemotherapy. The median patient age was about 63 years in each arm.

All patients in each arm received a least one induction dose and about 48% in each arm received at least some consolidation dosing. In all, 18% of patients in the ivosidenib arm and 19% in the enasidenib arm went on to maintenance.

Treatment discontinuations occurred in 55% of patients in the ivosidenib group and 84% in the enasidenib group. The primary reason for discontinuation included HSCT, adverse events, progressive disease, and death (one and four patients in the respective arms).

Adverse events of interest, regardless of attribution, included the IDH differentiation syndrome in two patients on ivosidenib and one on enasidenib, leukocytosis, QT interval prolongation, and increased blood bilirubin.

The 30-day and 60-day mortality rates were 5% and 8% in the ivosidenib arm and 5% and 9% in the enasidenib arm, respectively.

Best overall response rates (CR+CRi+CRp) among all patients were 80% in the ivosidenib arm and 72% in the enasidenib arm. In each trial arm, the response rates were higher among patients with de novo AML, compared with secondary AML.

Of 12 ivosidenib-treated patients who had IDH1-mutation clearance, 10 had clearance at the end of induction therapy, and 2 achieved clearance during or after consolidation. Of 15 ivosidenib-treated patients who became MRD negative, 12 had achieved it by the end of induction, and 3 became MRD negative during consolidation.

In the enasidenib arm, 15 patients had IDH2 mutation clearance (11 after induction, 4 during consolidation) and 9 became MRD negative (7 after induction and 2 during or after consolidation).

The probability of surviving to 1 year after the start of induction among ivosidenib-treated patients was 79%; the median overall survival had not been reached and was not estimable at the time of data cutoff. The probability of surviving to 1 year among patients in the enasidenib arm was 75%. In this group, too, median overall survival had not been reached.

The clinical benefit of adding either IDH inhibitor to induction, consolidation, and maintenance therapy for patients with newly diagnosed AML with IDH mutations will be further evaluated in a randomized, phase 3 trial, Dr. Stein said.

The study was funded by Agios Pharmaceuticals and Celgene. Dr. Stein reported consulting with those companies and others.

SOURCE: Stein EM et al. ASH 2018, Abstract 560.

SAN DIEGO – In patients with newly diagnosed acute myeloid leukemia (AML) bearing IDH1 or IDH2 mutations, combinations of either ivosidenib (Tibsovo, for IDH1) or enasidenib (Idhifa, for IDH2) with standard induction and consolidation regimens are safe and well tolerated and are associated with encouraging remission rates, results of a phase 1 trial indicate.

In the open-label, phase 1 trial, ivosidenib plus chemotherapy was associated with elimination of minimal residual disease (MRD) by flow cytometry in 88% of treated patients and with IDH1-mutation clearance in 41% of patients.

Enasidenib plus chemotherapy was associated with elimination of MRD in 45% of patients and with IDH2-mutation clearance in 25% of patients, said Eytan M. Stein, MD, from Memorial Sloan Kettering Cancer Center in New York.

“The overall survival rates are robust, with greater than 75% 1-year survival in both ivosidenib- and enasidenib-treated patients,” he said at the annual meeting of the American Society of Hematology.

Both ivosidenib and enasidenib are approved in the United States for treatment of patients with relapsed or refractory AML bearing either IDH1 or IDH2 mutations, respectively. In this trial, the investigators explored the therapeutic potential of the IDH inhibitors in patients with previously untreated disease.

Dr. Stein and his colleagues investigated combining each of the agents with standard induction therapy with either daunorubicin 60 mg/m² per day or idarubicin 12 mg/m² per day for 3 days, plus cytarabine 200 mg/m² per day for 7 days. Patients with IDH1 mutations received ivosidenib 500 mg once daily, and those with IDH2 mutations received enasidenib 100 mg once daily.

After induction, patients with a complete remission (CR), CR with incomplete recovery of hematologic counts (CRi), or CR with incomplete recovery of platelets (CRp) could receive up to four cycles of consolidation therapy while continuing the IDH inhibitor. Patients who completed consolidation or were ineligible for consolidation could continue on maintenance therapy with their assigned drug until the end of the study.

The drugs were discontinued in patients who went on to hematopoietic stem cell transplant.

The most frequent co-occurring baseline mutations were DNMT3A, NPM1, and NRAS for patients with IDH1 mutations, and DNMT3A, SRSF2, and ASXL1 for patients with IDH2 mutations.

A total of 60 patients were assigned to ivosidenib and chemotherapy and 93 were assigned to enasidenib/chemotherapy. The median patient age was about 63 years in each arm.

All patients in each arm received a least one induction dose and about 48% in each arm received at least some consolidation dosing. In all, 18% of patients in the ivosidenib arm and 19% in the enasidenib arm went on to maintenance.

Treatment discontinuations occurred in 55% of patients in the ivosidenib group and 84% in the enasidenib group. The primary reason for discontinuation included HSCT, adverse events, progressive disease, and death (one and four patients in the respective arms).

Adverse events of interest, regardless of attribution, included the IDH differentiation syndrome in two patients on ivosidenib and one on enasidenib, leukocytosis, QT interval prolongation, and increased blood bilirubin.

The 30-day and 60-day mortality rates were 5% and 8% in the ivosidenib arm and 5% and 9% in the enasidenib arm, respectively.

Best overall response rates (CR+CRi+CRp) among all patients were 80% in the ivosidenib arm and 72% in the enasidenib arm. In each trial arm, the response rates were higher among patients with de novo AML, compared with secondary AML.

Of 12 ivosidenib-treated patients who had IDH1-mutation clearance, 10 had clearance at the end of induction therapy, and 2 achieved clearance during or after consolidation. Of 15 ivosidenib-treated patients who became MRD negative, 12 had achieved it by the end of induction, and 3 became MRD negative during consolidation.

In the enasidenib arm, 15 patients had IDH2 mutation clearance (11 after induction, 4 during consolidation) and 9 became MRD negative (7 after induction and 2 during or after consolidation).

The probability of surviving to 1 year after the start of induction among ivosidenib-treated patients was 79%; the median overall survival had not been reached and was not estimable at the time of data cutoff. The probability of surviving to 1 year among patients in the enasidenib arm was 75%. In this group, too, median overall survival had not been reached.

The clinical benefit of adding either IDH inhibitor to induction, consolidation, and maintenance therapy for patients with newly diagnosed AML with IDH mutations will be further evaluated in a randomized, phase 3 trial, Dr. Stein said.

The study was funded by Agios Pharmaceuticals and Celgene. Dr. Stein reported consulting with those companies and others.

SOURCE: Stein EM et al. ASH 2018, Abstract 560.

SAN DIEGO – In patients with newly diagnosed acute myeloid leukemia (AML) bearing IDH1 or IDH2 mutations, combinations of either ivosidenib (Tibsovo, for IDH1) or enasidenib (Idhifa, for IDH2) with standard induction and consolidation regimens are safe and well tolerated and are associated with encouraging remission rates, results of a phase 1 trial indicate.

In the open-label, phase 1 trial, ivosidenib plus chemotherapy was associated with elimination of minimal residual disease (MRD) by flow cytometry in 88% of treated patients and with IDH1-mutation clearance in 41% of patients.

Enasidenib plus chemotherapy was associated with elimination of MRD in 45% of patients and with IDH2-mutation clearance in 25% of patients, said Eytan M. Stein, MD, from Memorial Sloan Kettering Cancer Center in New York.

“The overall survival rates are robust, with greater than 75% 1-year survival in both ivosidenib- and enasidenib-treated patients,” he said at the annual meeting of the American Society of Hematology.

Both ivosidenib and enasidenib are approved in the United States for treatment of patients with relapsed or refractory AML bearing either IDH1 or IDH2 mutations, respectively. In this trial, the investigators explored the therapeutic potential of the IDH inhibitors in patients with previously untreated disease.

Dr. Stein and his colleagues investigated combining each of the agents with standard induction therapy with either daunorubicin 60 mg/m² per day or idarubicin 12 mg/m² per day for 3 days, plus cytarabine 200 mg/m² per day for 7 days. Patients with IDH1 mutations received ivosidenib 500 mg once daily, and those with IDH2 mutations received enasidenib 100 mg once daily.

After induction, patients with a complete remission (CR), CR with incomplete recovery of hematologic counts (CRi), or CR with incomplete recovery of platelets (CRp) could receive up to four cycles of consolidation therapy while continuing the IDH inhibitor. Patients who completed consolidation or were ineligible for consolidation could continue on maintenance therapy with their assigned drug until the end of the study.

The drugs were discontinued in patients who went on to hematopoietic stem cell transplant.

The most frequent co-occurring baseline mutations were DNMT3A, NPM1, and NRAS for patients with IDH1 mutations, and DNMT3A, SRSF2, and ASXL1 for patients with IDH2 mutations.

A total of 60 patients were assigned to ivosidenib and chemotherapy and 93 were assigned to enasidenib/chemotherapy. The median patient age was about 63 years in each arm.

All patients in each arm received a least one induction dose and about 48% in each arm received at least some consolidation dosing. In all, 18% of patients in the ivosidenib arm and 19% in the enasidenib arm went on to maintenance.

Treatment discontinuations occurred in 55% of patients in the ivosidenib group and 84% in the enasidenib group. The primary reason for discontinuation included HSCT, adverse events, progressive disease, and death (one and four patients in the respective arms).

Adverse events of interest, regardless of attribution, included the IDH differentiation syndrome in two patients on ivosidenib and one on enasidenib, leukocytosis, QT interval prolongation, and increased blood bilirubin.

The 30-day and 60-day mortality rates were 5% and 8% in the ivosidenib arm and 5% and 9% in the enasidenib arm, respectively.

Best overall response rates (CR+CRi+CRp) among all patients were 80% in the ivosidenib arm and 72% in the enasidenib arm. In each trial arm, the response rates were higher among patients with de novo AML, compared with secondary AML.

Of 12 ivosidenib-treated patients who had IDH1-mutation clearance, 10 had clearance at the end of induction therapy, and 2 achieved clearance during or after consolidation. Of 15 ivosidenib-treated patients who became MRD negative, 12 had achieved it by the end of induction, and 3 became MRD negative during consolidation.

In the enasidenib arm, 15 patients had IDH2 mutation clearance (11 after induction, 4 during consolidation) and 9 became MRD negative (7 after induction and 2 during or after consolidation).

The probability of surviving to 1 year after the start of induction among ivosidenib-treated patients was 79%; the median overall survival had not been reached and was not estimable at the time of data cutoff. The probability of surviving to 1 year among patients in the enasidenib arm was 75%. In this group, too, median overall survival had not been reached.

The clinical benefit of adding either IDH inhibitor to induction, consolidation, and maintenance therapy for patients with newly diagnosed AML with IDH mutations will be further evaluated in a randomized, phase 3 trial, Dr. Stein said.

The study was funded by Agios Pharmaceuticals and Celgene. Dr. Stein reported consulting with those companies and others.

SOURCE: Stein EM et al. ASH 2018, Abstract 560.

©ASH/Scott Morgan 2018

SAN DIEGO—A shortened regimen of four cycles of rituximab (R) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in younger patients with favorable-risk diffuse large B-cell lymphoma (DLBCL), according to investigators of the FLYER trial.

In addition, the truncated regimen was associated with about a one-third reduction in non-hematologic adverse events.

Viola Poeschel, MD, of Saarland University Medical School in Homburg/Saar, Germany, reported results of this study on behalf of the German High-Grade Non-Hodgkin’s Lymphoma Study Group/German Lymphoma Alliance at the 2018 ASH Annual Meeting (abstract 781).

Among 588 evaluable patients younger than 60 with favorable-prognosis DLBCL, there were no significant differences in progression-free survival (PFS), event-free survival (EFS), or overall survival (OS) between patients who received four cycles of R-CHOP and those who received six cycles, Dr. Poeschel reported.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grade and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said.

The findings suggest that, for younger patients with favorable-prognosis DLBCL—defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm)—four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.

The investigators were prompted to look at the question of a shorter R-CHOP regimen by results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL patients had a 3-year PFS rate of 89%.

The FLYER trial (NCT00278421) was designed as a non-inferiority study to see whether, in a similar group of patients, reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.

At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the six-cycle group and 96% for the four-cycle group.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely non-inferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.

Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.

Treatment with six cycles was associated with more frequent hematologic adverse events than four cycles. Leukopenia of any grade occurred in 237 and 171 patients, respectively. Grade 3-4 leukopenia occurred in 110 and 80 patients, respectively.

Any-grade anemia occurred in 172 patients assigned to six cycles and 107 assigned to four cycles. Rates of grade 3-4 anemia were similar between the groups, as were rates of thrombocytopenia of any grade or grade 3-4.

Non-hematologic adverse events of any grade or grade 3-4 that were more frequent with six cycles included parasthesia, nausea, infection, vomiting, and mucositis.

The total number of non-hematologic adverse events was reduced by about one-third.

“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and, certainly, for this subgroup of patients, it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” said David Steensma, MD, of the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, Massachusetts.

Drs. Steensma and Poeschel both cautioned that the results of this study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.

“We can’t extend it to other subtypes of large-cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.

The study was supported by Deutsche Krebshilfe. Dr. Poeschel disclosed travel grants from Roche and Amgen. Dr. Steensma had no disclosures relevant to the study. 

©ASH/Scott Morgan 2018

SAN DIEGO—A shortened regimen of four cycles of rituximab (R) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in younger patients with favorable-risk diffuse large B-cell lymphoma (DLBCL), according to investigators of the FLYER trial.

In addition, the truncated regimen was associated with about a one-third reduction in non-hematologic adverse events.

Viola Poeschel, MD, of Saarland University Medical School in Homburg/Saar, Germany, reported results of this study on behalf of the German High-Grade Non-Hodgkin’s Lymphoma Study Group/German Lymphoma Alliance at the 2018 ASH Annual Meeting (abstract 781).

Among 588 evaluable patients younger than 60 with favorable-prognosis DLBCL, there were no significant differences in progression-free survival (PFS), event-free survival (EFS), or overall survival (OS) between patients who received four cycles of R-CHOP and those who received six cycles, Dr. Poeschel reported.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grade and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said.

The findings suggest that, for younger patients with favorable-prognosis DLBCL—defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm)—four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.

The investigators were prompted to look at the question of a shorter R-CHOP regimen by results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL patients had a 3-year PFS rate of 89%.

The FLYER trial (NCT00278421) was designed as a non-inferiority study to see whether, in a similar group of patients, reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.

At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the six-cycle group and 96% for the four-cycle group.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely non-inferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.

Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.

Treatment with six cycles was associated with more frequent hematologic adverse events than four cycles. Leukopenia of any grade occurred in 237 and 171 patients, respectively. Grade 3-4 leukopenia occurred in 110 and 80 patients, respectively.

Any-grade anemia occurred in 172 patients assigned to six cycles and 107 assigned to four cycles. Rates of grade 3-4 anemia were similar between the groups, as were rates of thrombocytopenia of any grade or grade 3-4.

Non-hematologic adverse events of any grade or grade 3-4 that were more frequent with six cycles included parasthesia, nausea, infection, vomiting, and mucositis.

The total number of non-hematologic adverse events was reduced by about one-third.

“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and, certainly, for this subgroup of patients, it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” said David Steensma, MD, of the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, Massachusetts.

Drs. Steensma and Poeschel both cautioned that the results of this study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.

“We can’t extend it to other subtypes of large-cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.

The study was supported by Deutsche Krebshilfe. Dr. Poeschel disclosed travel grants from Roche and Amgen. Dr. Steensma had no disclosures relevant to the study. 

©ASH/Scott Morgan 2018

SAN DIEGO—A shortened regimen of four cycles of rituximab (R) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in younger patients with favorable-risk diffuse large B-cell lymphoma (DLBCL), according to investigators of the FLYER trial.

In addition, the truncated regimen was associated with about a one-third reduction in non-hematologic adverse events.

Viola Poeschel, MD, of Saarland University Medical School in Homburg/Saar, Germany, reported results of this study on behalf of the German High-Grade Non-Hodgkin’s Lymphoma Study Group/German Lymphoma Alliance at the 2018 ASH Annual Meeting (abstract 781).

Among 588 evaluable patients younger than 60 with favorable-prognosis DLBCL, there were no significant differences in progression-free survival (PFS), event-free survival (EFS), or overall survival (OS) between patients who received four cycles of R-CHOP and those who received six cycles, Dr. Poeschel reported.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grade and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said.

The findings suggest that, for younger patients with favorable-prognosis DLBCL—defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm)—four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.

The investigators were prompted to look at the question of a shorter R-CHOP regimen by results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL patients had a 3-year PFS rate of 89%.

The FLYER trial (NCT00278421) was designed as a non-inferiority study to see whether, in a similar group of patients, reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.

At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the six-cycle group and 96% for the four-cycle group.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely non-inferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.

Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.

Treatment with six cycles was associated with more frequent hematologic adverse events than four cycles. Leukopenia of any grade occurred in 237 and 171 patients, respectively. Grade 3-4 leukopenia occurred in 110 and 80 patients, respectively.

Any-grade anemia occurred in 172 patients assigned to six cycles and 107 assigned to four cycles. Rates of grade 3-4 anemia were similar between the groups, as were rates of thrombocytopenia of any grade or grade 3-4.

Non-hematologic adverse events of any grade or grade 3-4 that were more frequent with six cycles included parasthesia, nausea, infection, vomiting, and mucositis.

The total number of non-hematologic adverse events was reduced by about one-third.

“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and, certainly, for this subgroup of patients, it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” said David Steensma, MD, of the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, Massachusetts.

Drs. Steensma and Poeschel both cautioned that the results of this study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.

“We can’t extend it to other subtypes of large-cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.

The study was supported by Deutsche Krebshilfe. Dr. Poeschel disclosed travel grants from Roche and Amgen. Dr. Steensma had no disclosures relevant to the study. 

© ASH/Luke Franke 2018

SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.

Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.

Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.

At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.

In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).

Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.

As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.

Fifty-four percent of patients who had achieved PR converted to CR.

The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 64%.

The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.

Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc. 

© ASH/Luke Franke 2018

SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.

Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.

Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.

At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.

In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).

Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.

As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.

Fifty-four percent of patients who had achieved PR converted to CR.

The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 64%.

The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.

Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc. 

© ASH/Luke Franke 2018

SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.

Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.

Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.

At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.

In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).

Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.

As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.

Fifty-four percent of patients who had achieved PR converted to CR.

The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 64%.

The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.

Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc. 

SAN DIEGO – Two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma who had early responses to chimeric antigen receptor T-cell (CAR T) therapy with tisagenlecleucel (Kymriah) remain in remission with no evidence of minimal residual disease, according to an updated analysis of the JULIET trial.

In the single-arm, open-label trial, the overall response rate after 19 months of follow-up was 54%, including 40% complete remissions and 14% partial remissions. The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.

Adverse events were similar to those previously reported and were manageable, according to investigator Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland.

In this video interview at the annual meeting of the American Society of Hematology, Dr. Maziarz discusses the promising results using CAR T cells in this difficult to treat population.

SAN DIEGO – Two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma who had early responses to chimeric antigen receptor T-cell (CAR T) therapy with tisagenlecleucel (Kymriah) remain in remission with no evidence of minimal residual disease, according to an updated analysis of the JULIET trial.

In the single-arm, open-label trial, the overall response rate after 19 months of follow-up was 54%, including 40% complete remissions and 14% partial remissions. The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.

Adverse events were similar to those previously reported and were manageable, according to investigator Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland.

In this video interview at the annual meeting of the American Society of Hematology, Dr. Maziarz discusses the promising results using CAR T cells in this difficult to treat population.

SAN DIEGO – Two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma who had early responses to chimeric antigen receptor T-cell (CAR T) therapy with tisagenlecleucel (Kymriah) remain in remission with no evidence of minimal residual disease, according to an updated analysis of the JULIET trial.

In the single-arm, open-label trial, the overall response rate after 19 months of follow-up was 54%, including 40% complete remissions and 14% partial remissions. The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.

Adverse events were similar to those previously reported and were manageable, according to investigator Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland.

In this video interview at the annual meeting of the American Society of Hematology, Dr. Maziarz discusses the promising results using CAR T cells in this difficult to treat population.

SAN DIEGO – Diversity of the gut microbiome, sampled either before or after an allogeneic hematopoietic cell transplant (HCT), is predictive of overall survival.

A multinational study of intestinal microbiota in the United States, Europe, and Japan showed that in all four geographic regions patients scheduled for HCT had about a 100% lower median diversity of intestinal bacteria, compared with healthy volunteers, and that enterococcal species predominated in the transplant candidates, reported Jonathan U. Peled, MD, PhD, from the bone marrow transplantation service at Memorial Sloan Kettering Cancer Center in New York.

The investigators also found that intestinal microbial diversity was significantly associated with overall survival following an HCT.

In a video interview at the annual meeting of the American Society of Hematology, Dr. Peled elaborated on the study findings and described potential pre- and posttransplant interventions that could improve results and increase survival following HCT.

Dr. Peled reported current or prior relationships with Seres Therapeutics, the Parker Institute for Cancer Immunotherapy, and Merck/Society for Immunotherapy of Cancer.

SAN DIEGO – Diversity of the gut microbiome, sampled either before or after an allogeneic hematopoietic cell transplant (HCT), is predictive of overall survival.

A multinational study of intestinal microbiota in the United States, Europe, and Japan showed that in all four geographic regions patients scheduled for HCT had about a 100% lower median diversity of intestinal bacteria, compared with healthy volunteers, and that enterococcal species predominated in the transplant candidates, reported Jonathan U. Peled, MD, PhD, from the bone marrow transplantation service at Memorial Sloan Kettering Cancer Center in New York.

The investigators also found that intestinal microbial diversity was significantly associated with overall survival following an HCT.

In a video interview at the annual meeting of the American Society of Hematology, Dr. Peled elaborated on the study findings and described potential pre- and posttransplant interventions that could improve results and increase survival following HCT.

Dr. Peled reported current or prior relationships with Seres Therapeutics, the Parker Institute for Cancer Immunotherapy, and Merck/Society for Immunotherapy of Cancer.

SAN DIEGO – Diversity of the gut microbiome, sampled either before or after an allogeneic hematopoietic cell transplant (HCT), is predictive of overall survival.

A multinational study of intestinal microbiota in the United States, Europe, and Japan showed that in all four geographic regions patients scheduled for HCT had about a 100% lower median diversity of intestinal bacteria, compared with healthy volunteers, and that enterococcal species predominated in the transplant candidates, reported Jonathan U. Peled, MD, PhD, from the bone marrow transplantation service at Memorial Sloan Kettering Cancer Center in New York.

The investigators also found that intestinal microbial diversity was significantly associated with overall survival following an HCT.

In a video interview at the annual meeting of the American Society of Hematology, Dr. Peled elaborated on the study findings and described potential pre- and posttransplant interventions that could improve results and increase survival following HCT.

Dr. Peled reported current or prior relationships with Seres Therapeutics, the Parker Institute for Cancer Immunotherapy, and Merck/Society for Immunotherapy of Cancer.

SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.

Neil Osterweil/MDedge News

After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.

The updated study results were published simultaneously online in the New England Journal of Medicine.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.

Interim results of the study were previously reported at the European Hematology Association Congress in 2017.

At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.

The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.

The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.

The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.

SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
 

SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.

Neil Osterweil/MDedge News

After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.

The updated study results were published simultaneously online in the New England Journal of Medicine.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.

Interim results of the study were previously reported at the European Hematology Association Congress in 2017.

At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.

The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.

The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.

The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.

SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
 

SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.

Neil Osterweil/MDedge News

After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.

The updated study results were published simultaneously online in the New England Journal of Medicine.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.

Interim results of the study were previously reported at the European Hematology Association Congress in 2017.

At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.

The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.

The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.

The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.

SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
 

SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in the FLYER trial reported.

Neil Osterweil/MDedge News

Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.

The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (Lancet Oncol. 2006 May;7[5]379-91). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.

At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.

Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.

R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.

Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.

Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.

As noted before, the total number of nonhematologic adverse events was reduced by about one-third.

Neil Osterweil/MDedge News

“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented David Steensma, MD, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.

Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.

“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.

The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.

SOURCE: Poeschel V et al. ASH 2018, Abstract 781.

SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in the FLYER trial reported.

Neil Osterweil/MDedge News

Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.

The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (Lancet Oncol. 2006 May;7[5]379-91). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.

At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.

Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.

R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.

Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.

Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.

As noted before, the total number of nonhematologic adverse events was reduced by about one-third.

Neil Osterweil/MDedge News

“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented David Steensma, MD, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.

Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.

“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.

The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.

SOURCE: Poeschel V et al. ASH 2018, Abstract 781.

SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in the FLYER trial reported.

Neil Osterweil/MDedge News

Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.

The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (Lancet Oncol. 2006 May;7[5]379-91). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.

At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.

Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.

R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.

Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.

Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.

As noted before, the total number of nonhematologic adverse events was reduced by about one-third.

Neil Osterweil/MDedge News

“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented David Steensma, MD, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.

Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.

“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.

The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.

SOURCE: Poeschel V et al. ASH 2018, Abstract 781.

SAN DIEGO – Patients aged younger than 60 years with favorable-prognosis diffuse large B-cell lymphoma who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) had progression-free, event-free, and overall survival rates comparable with those of patients assigned to six cycles, investigators in the FLYER trial reported.

The four-cycle regimen was associated with a marked reduction in adverse events, with an overall drop in nonhematologic malignancies of approximately one-third compared with the six-cycle regimen.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care.

In this video interview at the annual meeting of the American Society of Hematology, Viola Poeschel, MD, of Saarland University in Homburg, Germany, describes the patient population who may benefit from shorter duration therapy.

SAN DIEGO – Patients aged younger than 60 years with favorable-prognosis diffuse large B-cell lymphoma who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) had progression-free, event-free, and overall survival rates comparable with those of patients assigned to six cycles, investigators in the FLYER trial reported.

The four-cycle regimen was associated with a marked reduction in adverse events, with an overall drop in nonhematologic malignancies of approximately one-third compared with the six-cycle regimen.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care.

In this video interview at the annual meeting of the American Society of Hematology, Viola Poeschel, MD, of Saarland University in Homburg, Germany, describes the patient population who may benefit from shorter duration therapy.

SAN DIEGO – Patients aged younger than 60 years with favorable-prognosis diffuse large B-cell lymphoma who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) had progression-free, event-free, and overall survival rates comparable with those of patients assigned to six cycles, investigators in the FLYER trial reported.

The four-cycle regimen was associated with a marked reduction in adverse events, with an overall drop in nonhematologic malignancies of approximately one-third compared with the six-cycle regimen.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care.

In this video interview at the annual meeting of the American Society of Hematology, Viola Poeschel, MD, of Saarland University in Homburg, Germany, describes the patient population who may benefit from shorter duration therapy.