Lymphoma & Plasma Cell Disorders

LUGANO, SWITZERLAND – A combination of the Bruton’s tyrosine kinase (BTK) ibrutinib (Imbruvica) and the pan-phosphoinositide 3-kinase (PI3K) inhibitor buparlisib showed clinical activity superior to that of single-agent ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL).

In a phase I/IB dose escalation study and expansion cohort testing the combination in patients with diffuse large B cell lymphoma (DLBCL), follicular lymphoma, and MCL, the overall response rate (ORR) among patients with MCL was 100%, consisting of complete responses (CR) in 8 of 11 patients, and partial responses (PR) in 3 patients, reported Connie Lee Batlevi, MD, of Memorial Sloan Kettering Cancer Center in New York.

LUGANO, SWITZERLAND – A combination of the Bruton’s tyrosine kinase (BTK) ibrutinib (Imbruvica) and the pan-phosphoinositide 3-kinase (PI3K) inhibitor buparlisib showed clinical activity superior to that of single-agent ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL).

In a phase I/IB dose escalation study and expansion cohort testing the combination in patients with diffuse large B cell lymphoma (DLBCL), follicular lymphoma, and MCL, the overall response rate (ORR) among patients with MCL was 100%, consisting of complete responses (CR) in 8 of 11 patients, and partial responses (PR) in 3 patients, reported Connie Lee Batlevi, MD, of Memorial Sloan Kettering Cancer Center in New York.

LUGANO, SWITZERLAND – A combination of the Bruton’s tyrosine kinase (BTK) ibrutinib (Imbruvica) and the pan-phosphoinositide 3-kinase (PI3K) inhibitor buparlisib showed clinical activity superior to that of single-agent ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL).

In a phase I/IB dose escalation study and expansion cohort testing the combination in patients with diffuse large B cell lymphoma (DLBCL), follicular lymphoma, and MCL, the overall response rate (ORR) among patients with MCL was 100%, consisting of complete responses (CR) in 8 of 11 patients, and partial responses (PR) in 3 patients, reported Connie Lee Batlevi, MD, of Memorial Sloan Kettering Cancer Center in New York.

Micrograph showing HL

Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).

The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.

Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.

Brentuximab vedotin is currently not approved as a frontline therapy for HL.

“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.

Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.

Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.

ECHELON-1

ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.

The trial enrolled 1334 patients with histologically confirmed advanced HL.

The primary endpoint is mPFS by independent review facility.

The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.

They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.

Secondary endpoints include overall survival (OS), CR, and safety.

The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).

Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.

The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.

Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.

Febrile neutropenia was reduced with the use of prophylactic growth factors.

Peripheral neuropathy was managed through dose modifications.

Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.

The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.

Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.

Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.

For more on brentuximab vedotin, see the full prescribing informtion. 

Micrograph showing HL

Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).

The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.

Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.

Brentuximab vedotin is currently not approved as a frontline therapy for HL.

“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.

Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.

Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.

ECHELON-1

ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.

The trial enrolled 1334 patients with histologically confirmed advanced HL.

The primary endpoint is mPFS by independent review facility.

The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.

They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.

Secondary endpoints include overall survival (OS), CR, and safety.

The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).

Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.

The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.

Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.

Febrile neutropenia was reduced with the use of prophylactic growth factors.

Peripheral neuropathy was managed through dose modifications.

Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.

The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.

Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.

Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.

For more on brentuximab vedotin, see the full prescribing informtion. 

Micrograph showing HL

Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).

The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.

Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.

Brentuximab vedotin is currently not approved as a frontline therapy for HL.

“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.

Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.

Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.

ECHELON-1

ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.

The trial enrolled 1334 patients with histologically confirmed advanced HL.

The primary endpoint is mPFS by independent review facility.

The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.

They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.

Secondary endpoints include overall survival (OS), CR, and safety.

The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).

Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.

The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.

Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.

Febrile neutropenia was reduced with the use of prophylactic growth factors.

Peripheral neuropathy was managed through dose modifications.

Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.

The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.

Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.

Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.

For more on brentuximab vedotin, see the full prescribing informtion. 

LUGANO, SWITZERLAND – A novel combination of the anti-programmed death 1 (PD-1) checkpoint inhibitor pembrolizumab (Keytruda) and the anti-CD20 monoclonal antibody rituximab was associated with a high overall response rate (ORR) in patients with relapsed follicular lymphoma in a phase II clinical trial.

Among 20 patients evaluable for efficacy, the overall response rate to the combination was 65%, including 50% complete responses (CR) reported Loretta J. Nastoupil, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“Follicular lymphoma is probably one of the best examples of targeting the immune system and also one of the earliest examples. Over the last few years we’ve learned a great deal about the different mechanisms of not only negative impact on infiltrating T cells, but also immune escape and T-cell exhaustion,” she said at the International Conference on Malignant Lymphoma.

Although biopsies of follicular lymphoma tumors have demonstrated infiltration of anti-tumor T cells, these cells are typically impeded by immune checkpoints, including PD-1 and its ligand (PD-L1).

The use of anti-PD-1 checkpoint inhibitors such as pembrolizumab has been shown to enhance the function of antitumor T cells in follicular lymphoma, and blocking PD-1 on natural killer cells enhances the antibody-dependent cell-mediated cytotoxicity of the natural killer cells, she said.

Because rituximab, a mainstay of therapy for non-Hodgkin lymphomas, induces antibody-dependent cell-mediated cytotoxicity, the investigators reasoned that combining it with pembrolizumab would simultaneously and synergistically stimulate activation of innate and adaptive immunity.

They designed a phase II, single-arm study in 30 patients with relapsed follicular lymphoma following one or more prior lines of therapy. The patients also had to have rituximab-sensitive disease, defined as a complete response (CR) or partial response lasting for at least 6 months following the most recent rituximab-containing therapy.

The patients were treated with rituximab 375 mg/m² IV on days 1, 8, 15, and 22 of cycle 1, and pembrolizumab 200 mg IV every 3 weeks for up to 16 cycles starting on day 2 of cycle 1.

The investigators expected that the combination would improve ORR, the primary endpoint, to at least 60%, compared with 40% for historical controls treated with repeat courses of rituximab.

At the data cutoff for the interim analysis, 32 patients had been enrolled, 30 were evaluable for safety, and 20 for efficacy after a median follow-up of 8.2 months.

Among the 20 patients (median age 64) in the efficacy analysis, 10 (50%) had a CR, and 3 (15%) had a partial response, for an ORR of 65%. Three additional patients had stable disease, and four had disease progression as best responses.

Among the patients with CRs, the duration of response ranged from nearly 275 days to more than 600 days.

“This does appear to be durable, and it is time dependent in terms of response. We did see early response, and we also saw deepening of response over time,” Dr. Nastoupil said.

Four patients were discontinued from the study because of immune-related adverse events. All four patients had achieved a CR at the time of study removal, and all four have ongoing CRs.

Among the 30 patients evaluable for safety, there were no grade 4 adverse events, no deaths, and few grade 3 events. Most events were grade 1 or 2, and included fatigue, eye pain/blurred vision/watery eye, nausea and vomiting, diarrhea dyspnea, rash, cough, and lymphopenia.

The investigators also looked at potential biomarkers for response, including PD-L1 expression in tumors prior to treatment. They found in samples from three patients who went on to achieve CRs that PD-L1 expression in tumor cells was low, ranging from 0% to 8%, suggesting that PD-L1 expression may not be necessary to generate a response with the combination.

They then looked at the association between CD8-positive T effector cells and responses in 12 patients, and found that patients with higher levels of expression had better ORR and CR rates.

“These interim results warrant further investigation of this combination in follicular lymphoma, and an expansion to include patients with refractory follicular lymphoma is planned,” Dr. Nastoupil concluded.

The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.

LUGANO, SWITZERLAND – A novel combination of the anti-programmed death 1 (PD-1) checkpoint inhibitor pembrolizumab (Keytruda) and the anti-CD20 monoclonal antibody rituximab was associated with a high overall response rate (ORR) in patients with relapsed follicular lymphoma in a phase II clinical trial.

Among 20 patients evaluable for efficacy, the overall response rate to the combination was 65%, including 50% complete responses (CR) reported Loretta J. Nastoupil, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“Follicular lymphoma is probably one of the best examples of targeting the immune system and also one of the earliest examples. Over the last few years we’ve learned a great deal about the different mechanisms of not only negative impact on infiltrating T cells, but also immune escape and T-cell exhaustion,” she said at the International Conference on Malignant Lymphoma.

Although biopsies of follicular lymphoma tumors have demonstrated infiltration of anti-tumor T cells, these cells are typically impeded by immune checkpoints, including PD-1 and its ligand (PD-L1).

The use of anti-PD-1 checkpoint inhibitors such as pembrolizumab has been shown to enhance the function of antitumor T cells in follicular lymphoma, and blocking PD-1 on natural killer cells enhances the antibody-dependent cell-mediated cytotoxicity of the natural killer cells, she said.

Because rituximab, a mainstay of therapy for non-Hodgkin lymphomas, induces antibody-dependent cell-mediated cytotoxicity, the investigators reasoned that combining it with pembrolizumab would simultaneously and synergistically stimulate activation of innate and adaptive immunity.

They designed a phase II, single-arm study in 30 patients with relapsed follicular lymphoma following one or more prior lines of therapy. The patients also had to have rituximab-sensitive disease, defined as a complete response (CR) or partial response lasting for at least 6 months following the most recent rituximab-containing therapy.

The patients were treated with rituximab 375 mg/m² IV on days 1, 8, 15, and 22 of cycle 1, and pembrolizumab 200 mg IV every 3 weeks for up to 16 cycles starting on day 2 of cycle 1.

The investigators expected that the combination would improve ORR, the primary endpoint, to at least 60%, compared with 40% for historical controls treated with repeat courses of rituximab.

At the data cutoff for the interim analysis, 32 patients had been enrolled, 30 were evaluable for safety, and 20 for efficacy after a median follow-up of 8.2 months.

Among the 20 patients (median age 64) in the efficacy analysis, 10 (50%) had a CR, and 3 (15%) had a partial response, for an ORR of 65%. Three additional patients had stable disease, and four had disease progression as best responses.

Among the patients with CRs, the duration of response ranged from nearly 275 days to more than 600 days.

“This does appear to be durable, and it is time dependent in terms of response. We did see early response, and we also saw deepening of response over time,” Dr. Nastoupil said.

Four patients were discontinued from the study because of immune-related adverse events. All four patients had achieved a CR at the time of study removal, and all four have ongoing CRs.

Among the 30 patients evaluable for safety, there were no grade 4 adverse events, no deaths, and few grade 3 events. Most events were grade 1 or 2, and included fatigue, eye pain/blurred vision/watery eye, nausea and vomiting, diarrhea dyspnea, rash, cough, and lymphopenia.

The investigators also looked at potential biomarkers for response, including PD-L1 expression in tumors prior to treatment. They found in samples from three patients who went on to achieve CRs that PD-L1 expression in tumor cells was low, ranging from 0% to 8%, suggesting that PD-L1 expression may not be necessary to generate a response with the combination.

They then looked at the association between CD8-positive T effector cells and responses in 12 patients, and found that patients with higher levels of expression had better ORR and CR rates.

“These interim results warrant further investigation of this combination in follicular lymphoma, and an expansion to include patients with refractory follicular lymphoma is planned,” Dr. Nastoupil concluded.

The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.

LUGANO, SWITZERLAND – A novel combination of the anti-programmed death 1 (PD-1) checkpoint inhibitor pembrolizumab (Keytruda) and the anti-CD20 monoclonal antibody rituximab was associated with a high overall response rate (ORR) in patients with relapsed follicular lymphoma in a phase II clinical trial.

Among 20 patients evaluable for efficacy, the overall response rate to the combination was 65%, including 50% complete responses (CR) reported Loretta J. Nastoupil, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“Follicular lymphoma is probably one of the best examples of targeting the immune system and also one of the earliest examples. Over the last few years we’ve learned a great deal about the different mechanisms of not only negative impact on infiltrating T cells, but also immune escape and T-cell exhaustion,” she said at the International Conference on Malignant Lymphoma.

Although biopsies of follicular lymphoma tumors have demonstrated infiltration of anti-tumor T cells, these cells are typically impeded by immune checkpoints, including PD-1 and its ligand (PD-L1).

The use of anti-PD-1 checkpoint inhibitors such as pembrolizumab has been shown to enhance the function of antitumor T cells in follicular lymphoma, and blocking PD-1 on natural killer cells enhances the antibody-dependent cell-mediated cytotoxicity of the natural killer cells, she said.

Because rituximab, a mainstay of therapy for non-Hodgkin lymphomas, induces antibody-dependent cell-mediated cytotoxicity, the investigators reasoned that combining it with pembrolizumab would simultaneously and synergistically stimulate activation of innate and adaptive immunity.

They designed a phase II, single-arm study in 30 patients with relapsed follicular lymphoma following one or more prior lines of therapy. The patients also had to have rituximab-sensitive disease, defined as a complete response (CR) or partial response lasting for at least 6 months following the most recent rituximab-containing therapy.

The patients were treated with rituximab 375 mg/m² IV on days 1, 8, 15, and 22 of cycle 1, and pembrolizumab 200 mg IV every 3 weeks for up to 16 cycles starting on day 2 of cycle 1.

The investigators expected that the combination would improve ORR, the primary endpoint, to at least 60%, compared with 40% for historical controls treated with repeat courses of rituximab.

At the data cutoff for the interim analysis, 32 patients had been enrolled, 30 were evaluable for safety, and 20 for efficacy after a median follow-up of 8.2 months.

Among the 20 patients (median age 64) in the efficacy analysis, 10 (50%) had a CR, and 3 (15%) had a partial response, for an ORR of 65%. Three additional patients had stable disease, and four had disease progression as best responses.

Among the patients with CRs, the duration of response ranged from nearly 275 days to more than 600 days.

“This does appear to be durable, and it is time dependent in terms of response. We did see early response, and we also saw deepening of response over time,” Dr. Nastoupil said.

Four patients were discontinued from the study because of immune-related adverse events. All four patients had achieved a CR at the time of study removal, and all four have ongoing CRs.

Among the 30 patients evaluable for safety, there were no grade 4 adverse events, no deaths, and few grade 3 events. Most events were grade 1 or 2, and included fatigue, eye pain/blurred vision/watery eye, nausea and vomiting, diarrhea dyspnea, rash, cough, and lymphopenia.

The investigators also looked at potential biomarkers for response, including PD-L1 expression in tumors prior to treatment. They found in samples from three patients who went on to achieve CRs that PD-L1 expression in tumor cells was low, ranging from 0% to 8%, suggesting that PD-L1 expression may not be necessary to generate a response with the combination.

They then looked at the association between CD8-positive T effector cells and responses in 12 patients, and found that patients with higher levels of expression had better ORR and CR rates.

“These interim results warrant further investigation of this combination in follicular lymphoma, and an expansion to include patients with refractory follicular lymphoma is planned,” Dr. Nastoupil concluded.

The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.

MADRID – Two chimeric antigen receptor T cell (CAR-T) constructs are showing promising activity against treatment-refractory, aggressive forms of non-Hodgkin lymphoma in multicenter clinical trials.

In the ZUMA-1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 CAR-T product, was associated with an 82% objective response rate (ORR), including 54% complete responses, in patients with refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL), reported Yi Lin, MD, PhD, from the Mayo Clinic in Rochester Minnesota.

Nancy Baron/Frontline Medical News

ZUMA-1

Dr. Lin reported phase II results from ZUMA-1, investigating axi-cel at a target dose of 2 x 10⁶ cells per kilogram in 72 patients with refractory DLBCL (cohort 1), and 20 patients with refractory PMBCL or TFL (cohort 2).

The median patient age was 58 years. Patients had stage III or IV disease, 47% had International Prognostic Index (IPI) scores of 3-4, 77% had disease that was refractory to second-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

The axi-cel construct was successfully manufactured in 99% of patients, with an average turnaround time from apheresis to the clinical site of 17 days.

As noted before, the trial met its primary endpoint with an 82% ORR, consisting of 54% complete responses and 28% partial responses.

The median duration of response was 8.2 months, and for patients with complete responses the median duration has not been reached.

Median overall survival has also not been reached.

The treatment was generally safe, with only 13% of patients experiencing grade 3 or greater cytokine release syndrome (CRS), and 28% having grade 3 or greater neurologic events. The events were generally reversible, and the rates of each declined over time. The use of tociluzumab or steroids to control adverse events did not have a negative effect on responses, Dr. Lin said.

JULIET

In the ongoing JULIET study, patients with relapsed/refractory DLBCL after at least two prior lines of therapy and who are not candidates for stem cell transplants are enrolled.

Nancy Baron/Frontline Medical News

MADRID – Two chimeric antigen receptor T cell (CAR-T) constructs are showing promising activity against treatment-refractory, aggressive forms of non-Hodgkin lymphoma in multicenter clinical trials.

In the ZUMA-1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 CAR-T product, was associated with an 82% objective response rate (ORR), including 54% complete responses, in patients with refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL), reported Yi Lin, MD, PhD, from the Mayo Clinic in Rochester Minnesota.

Nancy Baron/Frontline Medical News

ZUMA-1

Dr. Lin reported phase II results from ZUMA-1, investigating axi-cel at a target dose of 2 x 10⁶ cells per kilogram in 72 patients with refractory DLBCL (cohort 1), and 20 patients with refractory PMBCL or TFL (cohort 2).

The median patient age was 58 years. Patients had stage III or IV disease, 47% had International Prognostic Index (IPI) scores of 3-4, 77% had disease that was refractory to second-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

The axi-cel construct was successfully manufactured in 99% of patients, with an average turnaround time from apheresis to the clinical site of 17 days.

As noted before, the trial met its primary endpoint with an 82% ORR, consisting of 54% complete responses and 28% partial responses.

The median duration of response was 8.2 months, and for patients with complete responses the median duration has not been reached.

Median overall survival has also not been reached.

The treatment was generally safe, with only 13% of patients experiencing grade 3 or greater cytokine release syndrome (CRS), and 28% having grade 3 or greater neurologic events. The events were generally reversible, and the rates of each declined over time. The use of tociluzumab or steroids to control adverse events did not have a negative effect on responses, Dr. Lin said.

JULIET

In the ongoing JULIET study, patients with relapsed/refractory DLBCL after at least two prior lines of therapy and who are not candidates for stem cell transplants are enrolled.

Nancy Baron/Frontline Medical News

MADRID – Two chimeric antigen receptor T cell (CAR-T) constructs are showing promising activity against treatment-refractory, aggressive forms of non-Hodgkin lymphoma in multicenter clinical trials.

In the ZUMA-1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 CAR-T product, was associated with an 82% objective response rate (ORR), including 54% complete responses, in patients with refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL), reported Yi Lin, MD, PhD, from the Mayo Clinic in Rochester Minnesota.

Nancy Baron/Frontline Medical News

ZUMA-1

Dr. Lin reported phase II results from ZUMA-1, investigating axi-cel at a target dose of 2 x 10⁶ cells per kilogram in 72 patients with refractory DLBCL (cohort 1), and 20 patients with refractory PMBCL or TFL (cohort 2).

The median patient age was 58 years. Patients had stage III or IV disease, 47% had International Prognostic Index (IPI) scores of 3-4, 77% had disease that was refractory to second-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

The axi-cel construct was successfully manufactured in 99% of patients, with an average turnaround time from apheresis to the clinical site of 17 days.

As noted before, the trial met its primary endpoint with an 82% ORR, consisting of 54% complete responses and 28% partial responses.

The median duration of response was 8.2 months, and for patients with complete responses the median duration has not been reached.

Median overall survival has also not been reached.

The treatment was generally safe, with only 13% of patients experiencing grade 3 or greater cytokine release syndrome (CRS), and 28% having grade 3 or greater neurologic events. The events were generally reversible, and the rates of each declined over time. The use of tociluzumab or steroids to control adverse events did not have a negative effect on responses, Dr. Lin said.

JULIET

In the ongoing JULIET study, patients with relapsed/refractory DLBCL after at least two prior lines of therapy and who are not candidates for stem cell transplants are enrolled.

Nancy Baron/Frontline Medical News

MADRID – Patients with advanced Hodgkin lymphoma who have a metabolic response after the first two cycles of extended-dose(e)BEACOPP can be spared from undergoing more than two additional cycles of the highly intensive and toxic regimen, investigators from the German Hodgkin Study Group (GHSG) contend.

Among 1,005 patients with Hodgkin lymphoma who had negative PET scans after the second cycle of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, prednisone, procarbazine), progression-free survival (PFS) was virtually identical whether patients were randomized to undergo a total of six-to-eight cycles or only four cycles, reported Peter Borchmann, MD, from the University of Cologne, Germany.

Neil Osterweil/Frontline Medical News

“For patients with negative PET-2 after initial treatment with eBEACOPP. Therapy with only two additional cycles of eBEACOPP is very effective, obviously, very safe, very short – it just takes 12 weeks – and it’s affordable,” he said.

“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far. That’s why we recommend this treatment, PET-guided extended BEACOPP in patients with newly diagnosed, advanced-stage Hodgkin lymphoma,” he added.

Although most patients in the United States with newly diagnosed Hodgkin lymphoma receive ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), BEACOPP is sometimes used for high-risk patients. BEACOPP is associated with considerable toxicities, however, including increased risk of secondary malignancies.

To see whether select patients could be cured with fewer cycles of therapy, the GHSG investigators designed the GHSG HD18 study in which patient with metabolic responses determined by fluorodeoxyglucose-PET after two eBEACOPP cycles were randomized to either two or six-to-eight additional cycles.

A total of 2,101 patients from the ages of 18-60 years with newly diagnosed advanced-stage Hodgkin lymphoma were enrolled from centers in Germany, Switzerland, Austria, the Czech Republic, and the Netherlands.

After the second cycle of therapy, patients underwent fluorodeoxyglucose-PET scans, and those with negative results were then randomized.

The trial was designed and powered for noninferiority of the shortened regimen, with a maximum allowable difference of 6%.

The trial met its primary endpoint and then some. After a median observation time of 53 months, the 5-year PFS rate for patients who received only four cycles was 91.2%, compared with 91.8% for patients who underwent six-to-eight cycles. As shown on a Kaplan-Meier curve, the two lines were superimposable and virtually impossible to tell apart.

Interestingly, 5-year overall survival was significantly better with the shorter, less toxic regimen, at 97.6% vs. 95.4%, respectively, translating into a hazard ratio favoring the shorter regimen of 0.36 (P = .006).

In addition, the four-cycle regimen was associated with fewer severe infections (8% vs 15%), and lower degrees of organ toxicity (8% vs. 18%). In addition, the rate of secondary acute myeloid leukemia or the myelodysplastic syndrome was 0.4% among the 501 patients treated with only four cycles, compared with 1.6% for the 504 patients who received six to eight cycles.

There were no treatment-related deaths among patients who underwent four cycles, compared with six deaths among patients treated with additional cycles.

In an interview, Dr. Borchmann said that the findings are likely to change the standard of care for those centers that use the BEACOPP regimen. He acknowledged that the regimen is highly toxic and requires intensive patient surveillance and management, which may be more practical in Europe where patients generally live closer to major cancer centers than in the more spacious United States.

The study was supported by German Cancer Aid, the Swiss State Secratariate for Education, Research and Innovation, and by Roche Pharma AG. Dr, Borchmann reported having no relevant disclosures.

MADRID – Patients with advanced Hodgkin lymphoma who have a metabolic response after the first two cycles of extended-dose(e)BEACOPP can be spared from undergoing more than two additional cycles of the highly intensive and toxic regimen, investigators from the German Hodgkin Study Group (GHSG) contend.

Among 1,005 patients with Hodgkin lymphoma who had negative PET scans after the second cycle of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, prednisone, procarbazine), progression-free survival (PFS) was virtually identical whether patients were randomized to undergo a total of six-to-eight cycles or only four cycles, reported Peter Borchmann, MD, from the University of Cologne, Germany.

Neil Osterweil/Frontline Medical News

“For patients with negative PET-2 after initial treatment with eBEACOPP. Therapy with only two additional cycles of eBEACOPP is very effective, obviously, very safe, very short – it just takes 12 weeks – and it’s affordable,” he said.

“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far. That’s why we recommend this treatment, PET-guided extended BEACOPP in patients with newly diagnosed, advanced-stage Hodgkin lymphoma,” he added.

Although most patients in the United States with newly diagnosed Hodgkin lymphoma receive ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), BEACOPP is sometimes used for high-risk patients. BEACOPP is associated with considerable toxicities, however, including increased risk of secondary malignancies.

To see whether select patients could be cured with fewer cycles of therapy, the GHSG investigators designed the GHSG HD18 study in which patient with metabolic responses determined by fluorodeoxyglucose-PET after two eBEACOPP cycles were randomized to either two or six-to-eight additional cycles.

A total of 2,101 patients from the ages of 18-60 years with newly diagnosed advanced-stage Hodgkin lymphoma were enrolled from centers in Germany, Switzerland, Austria, the Czech Republic, and the Netherlands.

After the second cycle of therapy, patients underwent fluorodeoxyglucose-PET scans, and those with negative results were then randomized.

The trial was designed and powered for noninferiority of the shortened regimen, with a maximum allowable difference of 6%.

The trial met its primary endpoint and then some. After a median observation time of 53 months, the 5-year PFS rate for patients who received only four cycles was 91.2%, compared with 91.8% for patients who underwent six-to-eight cycles. As shown on a Kaplan-Meier curve, the two lines were superimposable and virtually impossible to tell apart.

Interestingly, 5-year overall survival was significantly better with the shorter, less toxic regimen, at 97.6% vs. 95.4%, respectively, translating into a hazard ratio favoring the shorter regimen of 0.36 (P = .006).

In addition, the four-cycle regimen was associated with fewer severe infections (8% vs 15%), and lower degrees of organ toxicity (8% vs. 18%). In addition, the rate of secondary acute myeloid leukemia or the myelodysplastic syndrome was 0.4% among the 501 patients treated with only four cycles, compared with 1.6% for the 504 patients who received six to eight cycles.

There were no treatment-related deaths among patients who underwent four cycles, compared with six deaths among patients treated with additional cycles.

In an interview, Dr. Borchmann said that the findings are likely to change the standard of care for those centers that use the BEACOPP regimen. He acknowledged that the regimen is highly toxic and requires intensive patient surveillance and management, which may be more practical in Europe where patients generally live closer to major cancer centers than in the more spacious United States.

The study was supported by German Cancer Aid, the Swiss State Secratariate for Education, Research and Innovation, and by Roche Pharma AG. Dr, Borchmann reported having no relevant disclosures.

MADRID – Patients with advanced Hodgkin lymphoma who have a metabolic response after the first two cycles of extended-dose(e)BEACOPP can be spared from undergoing more than two additional cycles of the highly intensive and toxic regimen, investigators from the German Hodgkin Study Group (GHSG) contend.

Among 1,005 patients with Hodgkin lymphoma who had negative PET scans after the second cycle of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, prednisone, procarbazine), progression-free survival (PFS) was virtually identical whether patients were randomized to undergo a total of six-to-eight cycles or only four cycles, reported Peter Borchmann, MD, from the University of Cologne, Germany.

Neil Osterweil/Frontline Medical News

“For patients with negative PET-2 after initial treatment with eBEACOPP. Therapy with only two additional cycles of eBEACOPP is very effective, obviously, very safe, very short – it just takes 12 weeks – and it’s affordable,” he said.

“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far. That’s why we recommend this treatment, PET-guided extended BEACOPP in patients with newly diagnosed, advanced-stage Hodgkin lymphoma,” he added.

Although most patients in the United States with newly diagnosed Hodgkin lymphoma receive ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), BEACOPP is sometimes used for high-risk patients. BEACOPP is associated with considerable toxicities, however, including increased risk of secondary malignancies.

To see whether select patients could be cured with fewer cycles of therapy, the GHSG investigators designed the GHSG HD18 study in which patient with metabolic responses determined by fluorodeoxyglucose-PET after two eBEACOPP cycles were randomized to either two or six-to-eight additional cycles.

A total of 2,101 patients from the ages of 18-60 years with newly diagnosed advanced-stage Hodgkin lymphoma were enrolled from centers in Germany, Switzerland, Austria, the Czech Republic, and the Netherlands.

After the second cycle of therapy, patients underwent fluorodeoxyglucose-PET scans, and those with negative results were then randomized.

The trial was designed and powered for noninferiority of the shortened regimen, with a maximum allowable difference of 6%.

The trial met its primary endpoint and then some. After a median observation time of 53 months, the 5-year PFS rate for patients who received only four cycles was 91.2%, compared with 91.8% for patients who underwent six-to-eight cycles. As shown on a Kaplan-Meier curve, the two lines were superimposable and virtually impossible to tell apart.

Interestingly, 5-year overall survival was significantly better with the shorter, less toxic regimen, at 97.6% vs. 95.4%, respectively, translating into a hazard ratio favoring the shorter regimen of 0.36 (P = .006).

In addition, the four-cycle regimen was associated with fewer severe infections (8% vs 15%), and lower degrees of organ toxicity (8% vs. 18%). In addition, the rate of secondary acute myeloid leukemia or the myelodysplastic syndrome was 0.4% among the 501 patients treated with only four cycles, compared with 1.6% for the 504 patients who received six to eight cycles.

There were no treatment-related deaths among patients who underwent four cycles, compared with six deaths among patients treated with additional cycles.

In an interview, Dr. Borchmann said that the findings are likely to change the standard of care for those centers that use the BEACOPP regimen. He acknowledged that the regimen is highly toxic and requires intensive patient surveillance and management, which may be more practical in Europe where patients generally live closer to major cancer centers than in the more spacious United States.

The study was supported by German Cancer Aid, the Swiss State Secratariate for Education, Research and Innovation, and by Roche Pharma AG. Dr, Borchmann reported having no relevant disclosures.

Syringe

The US Food and Drug Administration (FDA) approved a new, subcutaneous (SC) formulation of rituximab with hyaluronidase human (Rituxan Hycela™).

The new formulation includes the same monoclonal antibody as intravenous rituximab, but is combined with an enzyme that helps to deliver rituximab under the skin.

The new treatment reduces administration time from 1.5 hours or more for intravenous rituximab to 5 to 7 minutes for the subcutaneous injection.

It is approved for use in adults with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL).

“[P]eople with 3 of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” said Sandra Horning, MD, chief medical officer of Genentech.

Rituxan Hycela is manufactured by Genentech, Inc, a member of the Roche Group, and jointly marketed by Biogen and Genentech USA, Inc.

“People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important,” she noted.

The FDA based its decision on results from 4 clinical studies:

• SABRINA (NCT01200758): Phase 3 combination study with chemotherapy and maintenance study in previously untreated FL
• SAWYER (NCT01292603): Phase 1b study in previously untreated CLL
• MabEase (NCT01649856): Phase 3 study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase 3 patient preference study in previously untreated FL and DLBCL

This last study showed that 77% of patients preferred subcutaneous over intravenous administration, primarily because it reduced administration time.

Together, these trials represented nearly 2,000 people and demonstrated that subcutaneous administration of rituximab/hyaluronidase resulted in non-inferior levels of rituximab in the blood compared to intravenous rituximab.

And the subcutaneous formulation also demonstrated comparable clinical efficacy outcomes to the intravenous formulation.

Patients must have had at least 1 full dose of intravenous rituximab without severe adverse reactions before receiving the subcutaneous injection. There is a higher risk of certain severe adverse reactions during the first infusion.

The safety profile of rituximab/hyaluronidase is also comparable to intravenous rituximab, except for cutaneous reactions.

The most common (≥20%) adverse reactions observed with rituximab/hyaluronidase were:

• In FL, infections, neutropenia, nausea, constipation, cough, and fatigue.
• In DLBCL, infections, neutropenia, alopecia, nausea, and anemia.
• In CLL, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and erythema at the injection site.

Rituxan Hycela will be available in the US within 1 to 2 weeks, according to the manufacturer. Intravenous rituximab will continue to be available.

A subcutaneous formulation of rituximab (MabThera) had previously been approved for use in European markets by the European Commission.

For further information on the new US formulation, see the full prescribing information. 

Syringe

The US Food and Drug Administration (FDA) approved a new, subcutaneous (SC) formulation of rituximab with hyaluronidase human (Rituxan Hycela™).

The new formulation includes the same monoclonal antibody as intravenous rituximab, but is combined with an enzyme that helps to deliver rituximab under the skin.

The new treatment reduces administration time from 1.5 hours or more for intravenous rituximab to 5 to 7 minutes for the subcutaneous injection.

It is approved for use in adults with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL).

“[P]eople with 3 of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” said Sandra Horning, MD, chief medical officer of Genentech.

Rituxan Hycela is manufactured by Genentech, Inc, a member of the Roche Group, and jointly marketed by Biogen and Genentech USA, Inc.

“People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important,” she noted.

The FDA based its decision on results from 4 clinical studies:

• SABRINA (NCT01200758): Phase 3 combination study with chemotherapy and maintenance study in previously untreated FL
• SAWYER (NCT01292603): Phase 1b study in previously untreated CLL
• MabEase (NCT01649856): Phase 3 study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase 3 patient preference study in previously untreated FL and DLBCL

This last study showed that 77% of patients preferred subcutaneous over intravenous administration, primarily because it reduced administration time.

Together, these trials represented nearly 2,000 people and demonstrated that subcutaneous administration of rituximab/hyaluronidase resulted in non-inferior levels of rituximab in the blood compared to intravenous rituximab.

And the subcutaneous formulation also demonstrated comparable clinical efficacy outcomes to the intravenous formulation.

Patients must have had at least 1 full dose of intravenous rituximab without severe adverse reactions before receiving the subcutaneous injection. There is a higher risk of certain severe adverse reactions during the first infusion.

The safety profile of rituximab/hyaluronidase is also comparable to intravenous rituximab, except for cutaneous reactions.

The most common (≥20%) adverse reactions observed with rituximab/hyaluronidase were:

• In FL, infections, neutropenia, nausea, constipation, cough, and fatigue.
• In DLBCL, infections, neutropenia, alopecia, nausea, and anemia.
• In CLL, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and erythema at the injection site.

Rituxan Hycela will be available in the US within 1 to 2 weeks, according to the manufacturer. Intravenous rituximab will continue to be available.

A subcutaneous formulation of rituximab (MabThera) had previously been approved for use in European markets by the European Commission.

For further information on the new US formulation, see the full prescribing information. 

Syringe

The US Food and Drug Administration (FDA) approved a new, subcutaneous (SC) formulation of rituximab with hyaluronidase human (Rituxan Hycela™).

The new formulation includes the same monoclonal antibody as intravenous rituximab, but is combined with an enzyme that helps to deliver rituximab under the skin.

The new treatment reduces administration time from 1.5 hours or more for intravenous rituximab to 5 to 7 minutes for the subcutaneous injection.

It is approved for use in adults with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL).

“[P]eople with 3 of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” said Sandra Horning, MD, chief medical officer of Genentech.

Rituxan Hycela is manufactured by Genentech, Inc, a member of the Roche Group, and jointly marketed by Biogen and Genentech USA, Inc.

“People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important,” she noted.

The FDA based its decision on results from 4 clinical studies:

• SABRINA (NCT01200758): Phase 3 combination study with chemotherapy and maintenance study in previously untreated FL
• SAWYER (NCT01292603): Phase 1b study in previously untreated CLL
• MabEase (NCT01649856): Phase 3 study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase 3 patient preference study in previously untreated FL and DLBCL

This last study showed that 77% of patients preferred subcutaneous over intravenous administration, primarily because it reduced administration time.

Together, these trials represented nearly 2,000 people and demonstrated that subcutaneous administration of rituximab/hyaluronidase resulted in non-inferior levels of rituximab in the blood compared to intravenous rituximab.

And the subcutaneous formulation also demonstrated comparable clinical efficacy outcomes to the intravenous formulation.

Patients must have had at least 1 full dose of intravenous rituximab without severe adverse reactions before receiving the subcutaneous injection. There is a higher risk of certain severe adverse reactions during the first infusion.

The safety profile of rituximab/hyaluronidase is also comparable to intravenous rituximab, except for cutaneous reactions.

The most common (≥20%) adverse reactions observed with rituximab/hyaluronidase were:

• In FL, infections, neutropenia, nausea, constipation, cough, and fatigue.
• In DLBCL, infections, neutropenia, alopecia, nausea, and anemia.
• In CLL, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and erythema at the injection site.

Rituxan Hycela will be available in the US within 1 to 2 weeks, according to the manufacturer. Intravenous rituximab will continue to be available.

A subcutaneous formulation of rituximab (MabThera) had previously been approved for use in European markets by the European Commission.

For further information on the new US formulation, see the full prescribing information. 

Photo by Rhoda Baer

A small study of 20 children aged 8 to 18 years with incurable or refractory cancers indicates children are reliable reporters of their symptoms and side effects.

The investigators collected reports from the children, who were enrolled on phase 1/2 clinical trials at 4 cancer centers and undergoing their first courses of chemotherapy.

The team assessed the feasibility and acceptability of collecting symptom, function, and quality of life (QOL) reports from the study participants.

The investigators also evaluated the measurement tool and interview questions at 2 time points.

They contend the youths’ self-reports potentially could be a new trial endpoint.

According to the investigators, only rarely do patient-reported outcomes (PROs) get incorporated into pediatric phase 1 or phase 2 trials.

And because these trials contribute to drug indications and labeling, the researchers decided to assess whether it was feasible to enroll young people and retain them in a PRO endeavor.

The researchers also assessed the reliability, validity, responsiveness, and range of the pediatric measures employed. They used the Patient-Reported Outcomes Measurement Information System (PROMIS) to capture statistically significant and clinically meaningful changes or minimally important differences (MIDs) in PROs.

Pamela S. Hinds, PhD, RN, of George Washington University in Washington, DC,  reported the findings on behalf of the Children's National Health System researchers in Cancer, the journal of the American Cancer Society.

"When experimental cancer drugs are studied, researchers collect details about how these promising therapies affect children's organs, but rarely do they ask the children themselves about symptoms they feel or the side effects they experience," Dr Hinds said.

"Without this crucial information, the full impact of the experimental treatment on the pediatric patient is likely underreported and clinicians are hobbled in their ability to effectively manage side effects," she added.

The team recruited children and adolescents enrolled in phase 1 safety or phase 2 efficacy trials at Children's National, Seattle Children's Hospital, Children's Hospital of Philadelphia, and Boston Children's Hospital.

Findings

Sixty percent of the participants were male and 70% were white.

Median age of the participants was 13.6 years: 7 (35%) were age 8 to 12, and 13 (65%) were 13 to 17.

Thirteen participants (65%) had solid tumors, 5 (25%) had brain tumors, and 2 (10%) had lymphoma.

A total of 29 patients were eligible to participate in the trial during 20 months of screening. Five parents and 2 patients declined to participate.

The remaining 22 patients who agreed to participate accounted for a 75.9% enrollment rate. Twenty of them (90.9%) participated at the first data time point, which was at the time of enrollment, and 77.3% participated 3 weeks later at time point 2.

The authors noted that refusals to enroll were more likely to come from parents (17.2%) than the eligible patients (8.3%).

And refusals only occurred when the self-report measures were not embedded in the clinical trial.

Of the 10 protocols represented, 7 patients were enrolled on the same protocol in which the PRO measures were embedded.

The researchers administered the 6-item short-form measures for the scales of Mobility, Pain, Fatigue, Depressive Symptoms, Anxiety, and Peer Relationships.

They asked the 4 open-ended questions—concerning QOL while receiving therapy and acceptability of the patient reporting—at time point 2.

At time point 1, 3 patients did not complete 3 PROMIS measures, for a person-missing rate of 15% and a measure-missing rate of 3.3%.

At the second time point, 2 patients did not complete 1 measure each, for a person-missing rate of 11.8% and a measure-missing rate of 2%.

All but one measure at time point 1 met the reliability criterion and all measures did so at time point 2.

The research team believes their findings support the feasibility and acceptability of completing quantitative and qualitative measures regarding symptom, function, and QOL experiences among children and adolescents with incurable cancer.

The researchers note the small study size and the number of parent refusals are limitations of the trial.

Nevertheless, they recommend embedding PROs in future pediatric oncology phase 1/2 trials. 

Photo by Rhoda Baer

A small study of 20 children aged 8 to 18 years with incurable or refractory cancers indicates children are reliable reporters of their symptoms and side effects.

The investigators collected reports from the children, who were enrolled on phase 1/2 clinical trials at 4 cancer centers and undergoing their first courses of chemotherapy.

The team assessed the feasibility and acceptability of collecting symptom, function, and quality of life (QOL) reports from the study participants.

The investigators also evaluated the measurement tool and interview questions at 2 time points.

They contend the youths’ self-reports potentially could be a new trial endpoint.

According to the investigators, only rarely do patient-reported outcomes (PROs) get incorporated into pediatric phase 1 or phase 2 trials.

And because these trials contribute to drug indications and labeling, the researchers decided to assess whether it was feasible to enroll young people and retain them in a PRO endeavor.

The researchers also assessed the reliability, validity, responsiveness, and range of the pediatric measures employed. They used the Patient-Reported Outcomes Measurement Information System (PROMIS) to capture statistically significant and clinically meaningful changes or minimally important differences (MIDs) in PROs.

Pamela S. Hinds, PhD, RN, of George Washington University in Washington, DC,  reported the findings on behalf of the Children's National Health System researchers in Cancer, the journal of the American Cancer Society.

"When experimental cancer drugs are studied, researchers collect details about how these promising therapies affect children's organs, but rarely do they ask the children themselves about symptoms they feel or the side effects they experience," Dr Hinds said.

"Without this crucial information, the full impact of the experimental treatment on the pediatric patient is likely underreported and clinicians are hobbled in their ability to effectively manage side effects," she added.

The team recruited children and adolescents enrolled in phase 1 safety or phase 2 efficacy trials at Children's National, Seattle Children's Hospital, Children's Hospital of Philadelphia, and Boston Children's Hospital.

Findings

Sixty percent of the participants were male and 70% were white.

Median age of the participants was 13.6 years: 7 (35%) were age 8 to 12, and 13 (65%) were 13 to 17.

Thirteen participants (65%) had solid tumors, 5 (25%) had brain tumors, and 2 (10%) had lymphoma.

A total of 29 patients were eligible to participate in the trial during 20 months of screening. Five parents and 2 patients declined to participate.

The remaining 22 patients who agreed to participate accounted for a 75.9% enrollment rate. Twenty of them (90.9%) participated at the first data time point, which was at the time of enrollment, and 77.3% participated 3 weeks later at time point 2.

The authors noted that refusals to enroll were more likely to come from parents (17.2%) than the eligible patients (8.3%).

And refusals only occurred when the self-report measures were not embedded in the clinical trial.

Of the 10 protocols represented, 7 patients were enrolled on the same protocol in which the PRO measures were embedded.

The researchers administered the 6-item short-form measures for the scales of Mobility, Pain, Fatigue, Depressive Symptoms, Anxiety, and Peer Relationships.

They asked the 4 open-ended questions—concerning QOL while receiving therapy and acceptability of the patient reporting—at time point 2.

At time point 1, 3 patients did not complete 3 PROMIS measures, for a person-missing rate of 15% and a measure-missing rate of 3.3%.

At the second time point, 2 patients did not complete 1 measure each, for a person-missing rate of 11.8% and a measure-missing rate of 2%.

All but one measure at time point 1 met the reliability criterion and all measures did so at time point 2.

The research team believes their findings support the feasibility and acceptability of completing quantitative and qualitative measures regarding symptom, function, and QOL experiences among children and adolescents with incurable cancer.

The researchers note the small study size and the number of parent refusals are limitations of the trial.

Nevertheless, they recommend embedding PROs in future pediatric oncology phase 1/2 trials. 

Photo by Rhoda Baer

A small study of 20 children aged 8 to 18 years with incurable or refractory cancers indicates children are reliable reporters of their symptoms and side effects.

The investigators collected reports from the children, who were enrolled on phase 1/2 clinical trials at 4 cancer centers and undergoing their first courses of chemotherapy.

The team assessed the feasibility and acceptability of collecting symptom, function, and quality of life (QOL) reports from the study participants.

The investigators also evaluated the measurement tool and interview questions at 2 time points.

They contend the youths’ self-reports potentially could be a new trial endpoint.

According to the investigators, only rarely do patient-reported outcomes (PROs) get incorporated into pediatric phase 1 or phase 2 trials.

And because these trials contribute to drug indications and labeling, the researchers decided to assess whether it was feasible to enroll young people and retain them in a PRO endeavor.

The researchers also assessed the reliability, validity, responsiveness, and range of the pediatric measures employed. They used the Patient-Reported Outcomes Measurement Information System (PROMIS) to capture statistically significant and clinically meaningful changes or minimally important differences (MIDs) in PROs.

Pamela S. Hinds, PhD, RN, of George Washington University in Washington, DC,  reported the findings on behalf of the Children's National Health System researchers in Cancer, the journal of the American Cancer Society.

"When experimental cancer drugs are studied, researchers collect details about how these promising therapies affect children's organs, but rarely do they ask the children themselves about symptoms they feel or the side effects they experience," Dr Hinds said.

"Without this crucial information, the full impact of the experimental treatment on the pediatric patient is likely underreported and clinicians are hobbled in their ability to effectively manage side effects," she added.

The team recruited children and adolescents enrolled in phase 1 safety or phase 2 efficacy trials at Children's National, Seattle Children's Hospital, Children's Hospital of Philadelphia, and Boston Children's Hospital.

Findings

Sixty percent of the participants were male and 70% were white.

Median age of the participants was 13.6 years: 7 (35%) were age 8 to 12, and 13 (65%) were 13 to 17.

Thirteen participants (65%) had solid tumors, 5 (25%) had brain tumors, and 2 (10%) had lymphoma.

A total of 29 patients were eligible to participate in the trial during 20 months of screening. Five parents and 2 patients declined to participate.

The remaining 22 patients who agreed to participate accounted for a 75.9% enrollment rate. Twenty of them (90.9%) participated at the first data time point, which was at the time of enrollment, and 77.3% participated 3 weeks later at time point 2.

The authors noted that refusals to enroll were more likely to come from parents (17.2%) than the eligible patients (8.3%).

And refusals only occurred when the self-report measures were not embedded in the clinical trial.

Of the 10 protocols represented, 7 patients were enrolled on the same protocol in which the PRO measures were embedded.

The researchers administered the 6-item short-form measures for the scales of Mobility, Pain, Fatigue, Depressive Symptoms, Anxiety, and Peer Relationships.

They asked the 4 open-ended questions—concerning QOL while receiving therapy and acceptability of the patient reporting—at time point 2.

At time point 1, 3 patients did not complete 3 PROMIS measures, for a person-missing rate of 15% and a measure-missing rate of 3.3%.

At the second time point, 2 patients did not complete 1 measure each, for a person-missing rate of 11.8% and a measure-missing rate of 2%.

All but one measure at time point 1 met the reliability criterion and all measures did so at time point 2.

The research team believes their findings support the feasibility and acceptability of completing quantitative and qualitative measures regarding symptom, function, and QOL experiences among children and adolescents with incurable cancer.

The researchers note the small study size and the number of parent refusals are limitations of the trial.

Nevertheless, they recommend embedding PROs in future pediatric oncology phase 1/2 trials. 

MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.

The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.

MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.

The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.

MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.

The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.

Lugano, Switzerland – It’s not the end of chemotherapy for young patients with newly diagnosed mantle cell lymphoma (MCL), but it’s a start.

For these patients, induction with a combination of ibrutinib and rituximab, followed by shorter cycles of chemoimmunotherapy, was associated in an early study with an objective response rate of 100%, including 90% complete responses (CR), reported Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first time for a chemo-free therapy – ibrutinib/rituximab – to achieve an overall response rate of 100%. This has an unprecedented efficacy in the frontline in young patients with mantle-cell lymphoma,” he said at the 14th International Congress on Malignant Lymphoma.

In patients with relapsed or refractory MCL, the combination of ibrutinib and rituximab has been associated with durable responses in 88% of patients. The success of the combination suggests that fit patients younger than age 65 years with newly diagnosed MCL might benefit from a chemotherapy-free induction regimen with ibrutinib and rituximab, followed by consolidation with a short but intense course of chemoimmunotherapy, Dr. Wang said.

He presented updated results from the phase II Window I study, first results of which were reported at the 2016 meeting of the American Society of Hematology.

“Frontline therapy is the most important therapy for mantle cell lymphoma, because mantle cell lymphoma cells are most vulnerable to frontline attack. If the frontline therapy is good enough, it could kill all the mantle cell lymphoma cells, therefore leaving no chance for secondary resistance, and thereby (resulting in) long-term survival. And it is really my belief that if we ideally optimized the frontline therapy, that would be a shortcut to a cure,” he said.

To test this idea, Dr. Wang and MD Anderson colleagues initiated a phase II trial at their institution with 50 patients age 65 years or under with newly diagnosed, CD20-positive and Cyclin D1-positive MCL.

A total of 50 patients age 65 years or younger (median age 54) with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib 560 mg, plus rituximab 375 mg/m² administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), alternating every 28 days with rituximab plus high-dose methotrexate–cytarabine.

Patients who had complete responses to induction received four cycles of chemoimmunotherapy, while those who experienced disease progression and those who had partial responses received chemoimmunotherapy for two cycles beyond the point of complete remissions.

At the time of the presentation, all 50 patients were evaluable for the induction phase (part 2), and 47 were evaluable for both induction and consolidation (part 2) .Of the evaluable patients, the overall response rate (ORR) to chemotherapy-free induction therapy alone (Part 1 ) was 100% (50), with CR in 90% of patients and partial responses (PR) in 10%. Of the 47 patients evaluable for part 2 (chemoimmunotherapy), all had CRs, for an ORR of 100%.

Dr. Wang noted that one patient had a dramatic radiographic reduction in spleen size following just two cycles of chemotherapy-free induction, and two other patients had similar reductions after four and six cycles, respectively.

After a median follow-up of 15.9 months, neither the median duration of response, progression-free survival, nor overall survival have been reached. There have been no deaths and only one case of disease progression after one year of therapy.

The patients generally tolerated the regimen very well, Dr. Wang said. There were no cases of lymphocytosis, bleeding, or atrial fibrillation after 332 combined cycles.

Nonhematological adverse events were primarily grade 1 or 2. Grade 3 fatigue was reported in approximately 10% of patients. There were no grade 4 adverse events.

“This study may provide a window of opportunity to reduce the frontline therapies and reduce the long-term toxicities such as secondary malignancies.” Dr. Wang said.

He acknowledged that four cycles of intensive chemotherapy is still toxic and that further efforts to reduce these toxicities are needed. The investigators are currently planning the Window II study, in which a fraction of patients will be treated with no chemotherapy at all, he said.­­­­

The study was supported by Pharmacyclics and Janssen. Dr. Wang disclosed receiving research grants and honoraria and serving as a consultant for the companies.

Lugano, Switzerland – It’s not the end of chemotherapy for young patients with newly diagnosed mantle cell lymphoma (MCL), but it’s a start.

For these patients, induction with a combination of ibrutinib and rituximab, followed by shorter cycles of chemoimmunotherapy, was associated in an early study with an objective response rate of 100%, including 90% complete responses (CR), reported Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first time for a chemo-free therapy – ibrutinib/rituximab – to achieve an overall response rate of 100%. This has an unprecedented efficacy in the frontline in young patients with mantle-cell lymphoma,” he said at the 14th International Congress on Malignant Lymphoma.

In patients with relapsed or refractory MCL, the combination of ibrutinib and rituximab has been associated with durable responses in 88% of patients. The success of the combination suggests that fit patients younger than age 65 years with newly diagnosed MCL might benefit from a chemotherapy-free induction regimen with ibrutinib and rituximab, followed by consolidation with a short but intense course of chemoimmunotherapy, Dr. Wang said.

He presented updated results from the phase II Window I study, first results of which were reported at the 2016 meeting of the American Society of Hematology.

“Frontline therapy is the most important therapy for mantle cell lymphoma, because mantle cell lymphoma cells are most vulnerable to frontline attack. If the frontline therapy is good enough, it could kill all the mantle cell lymphoma cells, therefore leaving no chance for secondary resistance, and thereby (resulting in) long-term survival. And it is really my belief that if we ideally optimized the frontline therapy, that would be a shortcut to a cure,” he said.

To test this idea, Dr. Wang and MD Anderson colleagues initiated a phase II trial at their institution with 50 patients age 65 years or under with newly diagnosed, CD20-positive and Cyclin D1-positive MCL.

A total of 50 patients age 65 years or younger (median age 54) with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib 560 mg, plus rituximab 375 mg/m² administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), alternating every 28 days with rituximab plus high-dose methotrexate–cytarabine.

Patients who had complete responses to induction received four cycles of chemoimmunotherapy, while those who experienced disease progression and those who had partial responses received chemoimmunotherapy for two cycles beyond the point of complete remissions.

At the time of the presentation, all 50 patients were evaluable for the induction phase (part 2), and 47 were evaluable for both induction and consolidation (part 2) .Of the evaluable patients, the overall response rate (ORR) to chemotherapy-free induction therapy alone (Part 1 ) was 100% (50), with CR in 90% of patients and partial responses (PR) in 10%. Of the 47 patients evaluable for part 2 (chemoimmunotherapy), all had CRs, for an ORR of 100%.

Dr. Wang noted that one patient had a dramatic radiographic reduction in spleen size following just two cycles of chemotherapy-free induction, and two other patients had similar reductions after four and six cycles, respectively.

After a median follow-up of 15.9 months, neither the median duration of response, progression-free survival, nor overall survival have been reached. There have been no deaths and only one case of disease progression after one year of therapy.

The patients generally tolerated the regimen very well, Dr. Wang said. There were no cases of lymphocytosis, bleeding, or atrial fibrillation after 332 combined cycles.

Nonhematological adverse events were primarily grade 1 or 2. Grade 3 fatigue was reported in approximately 10% of patients. There were no grade 4 adverse events.

“This study may provide a window of opportunity to reduce the frontline therapies and reduce the long-term toxicities such as secondary malignancies.” Dr. Wang said.

He acknowledged that four cycles of intensive chemotherapy is still toxic and that further efforts to reduce these toxicities are needed. The investigators are currently planning the Window II study, in which a fraction of patients will be treated with no chemotherapy at all, he said.­­­­

The study was supported by Pharmacyclics and Janssen. Dr. Wang disclosed receiving research grants and honoraria and serving as a consultant for the companies.

Lugano, Switzerland – It’s not the end of chemotherapy for young patients with newly diagnosed mantle cell lymphoma (MCL), but it’s a start.

For these patients, induction with a combination of ibrutinib and rituximab, followed by shorter cycles of chemoimmunotherapy, was associated in an early study with an objective response rate of 100%, including 90% complete responses (CR), reported Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first time for a chemo-free therapy – ibrutinib/rituximab – to achieve an overall response rate of 100%. This has an unprecedented efficacy in the frontline in young patients with mantle-cell lymphoma,” he said at the 14th International Congress on Malignant Lymphoma.

In patients with relapsed or refractory MCL, the combination of ibrutinib and rituximab has been associated with durable responses in 88% of patients. The success of the combination suggests that fit patients younger than age 65 years with newly diagnosed MCL might benefit from a chemotherapy-free induction regimen with ibrutinib and rituximab, followed by consolidation with a short but intense course of chemoimmunotherapy, Dr. Wang said.

He presented updated results from the phase II Window I study, first results of which were reported at the 2016 meeting of the American Society of Hematology.

“Frontline therapy is the most important therapy for mantle cell lymphoma, because mantle cell lymphoma cells are most vulnerable to frontline attack. If the frontline therapy is good enough, it could kill all the mantle cell lymphoma cells, therefore leaving no chance for secondary resistance, and thereby (resulting in) long-term survival. And it is really my belief that if we ideally optimized the frontline therapy, that would be a shortcut to a cure,” he said.

To test this idea, Dr. Wang and MD Anderson colleagues initiated a phase II trial at their institution with 50 patients age 65 years or under with newly diagnosed, CD20-positive and Cyclin D1-positive MCL.

A total of 50 patients age 65 years or younger (median age 54) with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib 560 mg, plus rituximab 375 mg/m² administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), alternating every 28 days with rituximab plus high-dose methotrexate–cytarabine.

Patients who had complete responses to induction received four cycles of chemoimmunotherapy, while those who experienced disease progression and those who had partial responses received chemoimmunotherapy for two cycles beyond the point of complete remissions.

At the time of the presentation, all 50 patients were evaluable for the induction phase (part 2), and 47 were evaluable for both induction and consolidation (part 2) .Of the evaluable patients, the overall response rate (ORR) to chemotherapy-free induction therapy alone (Part 1 ) was 100% (50), with CR in 90% of patients and partial responses (PR) in 10%. Of the 47 patients evaluable for part 2 (chemoimmunotherapy), all had CRs, for an ORR of 100%.

Dr. Wang noted that one patient had a dramatic radiographic reduction in spleen size following just two cycles of chemotherapy-free induction, and two other patients had similar reductions after four and six cycles, respectively.

After a median follow-up of 15.9 months, neither the median duration of response, progression-free survival, nor overall survival have been reached. There have been no deaths and only one case of disease progression after one year of therapy.

The patients generally tolerated the regimen very well, Dr. Wang said. There were no cases of lymphocytosis, bleeding, or atrial fibrillation after 332 combined cycles.

Nonhematological adverse events were primarily grade 1 or 2. Grade 3 fatigue was reported in approximately 10% of patients. There were no grade 4 adverse events.

“This study may provide a window of opportunity to reduce the frontline therapies and reduce the long-term toxicities such as secondary malignancies.” Dr. Wang said.

He acknowledged that four cycles of intensive chemotherapy is still toxic and that further efforts to reduce these toxicities are needed. The investigators are currently planning the Window II study, in which a fraction of patients will be treated with no chemotherapy at all, he said.­­­­

The study was supported by Pharmacyclics and Janssen. Dr. Wang disclosed receiving research grants and honoraria and serving as a consultant for the companies.

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.” 

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.” 

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.”