Non-Hodgkin Lymphoma Hub

Combination chemotherapy with bendamustine, gemcitabine, and vinorelbine can induce high complete response rates among patients with relapsed or refractory Hodgkin lymphoma (HL) who are candidates for autologous stem cell transplantation, final results of a phase II study show.

Among 59 patients enrolled in the multicenter study, 49 (83%) had responses, including 43 (73%) who achieved a complete response (CR), and 6 (10%) who had a partial response after 4 cycles of chemotherapy with bendamustine (Treanda), gemcitabine (Gemzar), and vinorelbine (BeGEV).

Of the 49 patients with responses, 43 went on to autologous stem cell transplant (ASCT), reported Armando Santoro, MD, from the Humanitas Cancer Center in Rozzano, Italy.

“These findings provide a strong rationale for further development of the BeGEV regimen,” the investigators wrote in a study published online in the Journal of Clinical Oncology (2016 Jul 5. doi: 10.1200/JCO.2016.66.4466).

The investigators had previously shown that a regimen of ifosfamide, gemcitabine, and vinorelbine (IEGV) as salvage chemotherapy prior to ASCT was associated with an 81% overall response rate (ORR) 54% CR rate.

Because bendamustine has shown good activity as monotherapy against relapsed/refractory HL, they conducted a phase II study with an IEGV-like regimen in which bendamustine would be substituted for ifosfamide, to determine whether the substitution could improve response rates.

They enrolled 59 consecutive patients aged 18 years and older with HL that had relapsed or was refractory to one previous line of chemotherapy. Patients were treated with gemcitabine 800 mg/m² on days 1 and 4, vinorelbine 20 mg/m² on day 1, and bendamustine 90 mg/m² on days 2 and 3. Patients also received prednisolone 100 mg/day for days 1 to 4. The patients were treated for four 21-day cycles.

Patients who achieved either a complete or partial response after completion of the four planned cycles then underwent myeloablative therapy with carmustine or fotemustine plus etoposide, cytarabine, and melphalan, followed by reinfusion of mobilized CD34-positive circulating stem cells.

Grade 3 or 4 hematologic toxicities included thrombocytopenia and neutropenia, which occurred in eight patients each. Fifty-five of 57 total evaluable patients had successful mobilization and harvesting of CD34-positive cells, and, as noted before, 43 went on to ASCT.

After a median follow-up of 29 months, the 2-year progression-free survival (PFS) rate for the total population was 62%, and the overall survival rates was nearly 78%. For patients who went on to ASCT, the 2-year PFS rate was 81%, and the 2-year survival rate was 89%.

The authors noted that BeGV was associated with higher CR rates than IEGV, and with “excellent” stem cell mobilization activity and engraftment. Additionally, BeGV has a favorable toxicity profile, because of the absence of ifosfamide which is known to significantly increase risk for hemorrhagic cystitis.

“Because the number of novel agents that may be added in the pretransplantation therapy setting is growing, direct comparisons of combinations incorporating novel agents with BeGEV and other regimens will be necessary to identify the best salvage strategy for relapsed and refractory HL,” the authors wrote.

The study was supported in part by a grant from Mundipharma Pharmaceuticals. Two coauthors disclosed consulting/advisory roles and travel accommodations and expenses from the company.

Combination chemotherapy with bendamustine, gemcitabine, and vinorelbine can induce high complete response rates among patients with relapsed or refractory Hodgkin lymphoma (HL) who are candidates for autologous stem cell transplantation, final results of a phase II study show.

Among 59 patients enrolled in the multicenter study, 49 (83%) had responses, including 43 (73%) who achieved a complete response (CR), and 6 (10%) who had a partial response after 4 cycles of chemotherapy with bendamustine (Treanda), gemcitabine (Gemzar), and vinorelbine (BeGEV).

Of the 49 patients with responses, 43 went on to autologous stem cell transplant (ASCT), reported Armando Santoro, MD, from the Humanitas Cancer Center in Rozzano, Italy.

“These findings provide a strong rationale for further development of the BeGEV regimen,” the investigators wrote in a study published online in the Journal of Clinical Oncology (2016 Jul 5. doi: 10.1200/JCO.2016.66.4466).

The investigators had previously shown that a regimen of ifosfamide, gemcitabine, and vinorelbine (IEGV) as salvage chemotherapy prior to ASCT was associated with an 81% overall response rate (ORR) 54% CR rate.

Because bendamustine has shown good activity as monotherapy against relapsed/refractory HL, they conducted a phase II study with an IEGV-like regimen in which bendamustine would be substituted for ifosfamide, to determine whether the substitution could improve response rates.

They enrolled 59 consecutive patients aged 18 years and older with HL that had relapsed or was refractory to one previous line of chemotherapy. Patients were treated with gemcitabine 800 mg/m² on days 1 and 4, vinorelbine 20 mg/m² on day 1, and bendamustine 90 mg/m² on days 2 and 3. Patients also received prednisolone 100 mg/day for days 1 to 4. The patients were treated for four 21-day cycles.

Patients who achieved either a complete or partial response after completion of the four planned cycles then underwent myeloablative therapy with carmustine or fotemustine plus etoposide, cytarabine, and melphalan, followed by reinfusion of mobilized CD34-positive circulating stem cells.

Grade 3 or 4 hematologic toxicities included thrombocytopenia and neutropenia, which occurred in eight patients each. Fifty-five of 57 total evaluable patients had successful mobilization and harvesting of CD34-positive cells, and, as noted before, 43 went on to ASCT.

After a median follow-up of 29 months, the 2-year progression-free survival (PFS) rate for the total population was 62%, and the overall survival rates was nearly 78%. For patients who went on to ASCT, the 2-year PFS rate was 81%, and the 2-year survival rate was 89%.

The authors noted that BeGV was associated with higher CR rates than IEGV, and with “excellent” stem cell mobilization activity and engraftment. Additionally, BeGV has a favorable toxicity profile, because of the absence of ifosfamide which is known to significantly increase risk for hemorrhagic cystitis.

“Because the number of novel agents that may be added in the pretransplantation therapy setting is growing, direct comparisons of combinations incorporating novel agents with BeGEV and other regimens will be necessary to identify the best salvage strategy for relapsed and refractory HL,” the authors wrote.

The study was supported in part by a grant from Mundipharma Pharmaceuticals. Two coauthors disclosed consulting/advisory roles and travel accommodations and expenses from the company.

Combination chemotherapy with bendamustine, gemcitabine, and vinorelbine can induce high complete response rates among patients with relapsed or refractory Hodgkin lymphoma (HL) who are candidates for autologous stem cell transplantation, final results of a phase II study show.

Among 59 patients enrolled in the multicenter study, 49 (83%) had responses, including 43 (73%) who achieved a complete response (CR), and 6 (10%) who had a partial response after 4 cycles of chemotherapy with bendamustine (Treanda), gemcitabine (Gemzar), and vinorelbine (BeGEV).

Of the 49 patients with responses, 43 went on to autologous stem cell transplant (ASCT), reported Armando Santoro, MD, from the Humanitas Cancer Center in Rozzano, Italy.

“These findings provide a strong rationale for further development of the BeGEV regimen,” the investigators wrote in a study published online in the Journal of Clinical Oncology (2016 Jul 5. doi: 10.1200/JCO.2016.66.4466).

The investigators had previously shown that a regimen of ifosfamide, gemcitabine, and vinorelbine (IEGV) as salvage chemotherapy prior to ASCT was associated with an 81% overall response rate (ORR) 54% CR rate.

Because bendamustine has shown good activity as monotherapy against relapsed/refractory HL, they conducted a phase II study with an IEGV-like regimen in which bendamustine would be substituted for ifosfamide, to determine whether the substitution could improve response rates.

They enrolled 59 consecutive patients aged 18 years and older with HL that had relapsed or was refractory to one previous line of chemotherapy. Patients were treated with gemcitabine 800 mg/m² on days 1 and 4, vinorelbine 20 mg/m² on day 1, and bendamustine 90 mg/m² on days 2 and 3. Patients also received prednisolone 100 mg/day for days 1 to 4. The patients were treated for four 21-day cycles.

Patients who achieved either a complete or partial response after completion of the four planned cycles then underwent myeloablative therapy with carmustine or fotemustine plus etoposide, cytarabine, and melphalan, followed by reinfusion of mobilized CD34-positive circulating stem cells.

Grade 3 or 4 hematologic toxicities included thrombocytopenia and neutropenia, which occurred in eight patients each. Fifty-five of 57 total evaluable patients had successful mobilization and harvesting of CD34-positive cells, and, as noted before, 43 went on to ASCT.

After a median follow-up of 29 months, the 2-year progression-free survival (PFS) rate for the total population was 62%, and the overall survival rates was nearly 78%. For patients who went on to ASCT, the 2-year PFS rate was 81%, and the 2-year survival rate was 89%.

The authors noted that BeGV was associated with higher CR rates than IEGV, and with “excellent” stem cell mobilization activity and engraftment. Additionally, BeGV has a favorable toxicity profile, because of the absence of ifosfamide which is known to significantly increase risk for hemorrhagic cystitis.

“Because the number of novel agents that may be added in the pretransplantation therapy setting is growing, direct comparisons of combinations incorporating novel agents with BeGEV and other regimens will be necessary to identify the best salvage strategy for relapsed and refractory HL,” the authors wrote.

The study was supported in part by a grant from Mundipharma Pharmaceuticals. Two coauthors disclosed consulting/advisory roles and travel accommodations and expenses from the company.

PD-1 checkpoint blockade via pembrolizumab is a potential option for classical Hodgkin’s lymphoma that progressed despite brentuximab vedotin therapy, based on a phase Ib, single-arm, open-label, industry-sponsored study of 31 patients.

After a median follow-up of 17 months, five (16%) patients achieved complete remission (90% confidence interval, 7%-31%), and 15 (48%) patients achieved partial remission (90% CI, 33%-64%), for an overall response rate of 65% (48%-79%). Furthermore, 70% of responses lasted at least 24 weeks, reported Philippe Armand, MD, of Dana-Farber Cancer Institute, Boston, and his associates.

“Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies,” they added. “Yet partial responses can be durable, suggesting that the achievement of complete response with checkpoint blockade is not necessary to derive significant clinical benefit.”

Pembrolizumab (Keytruda) is a humanized, highly selective IgG4 anti-PD-1 (programmed death-1) monoclonal antibody approved in the United States for patients with unresectable or metastatic melanoma or metastatic PDL-1 expressing non–small cell lung cancer. Tumor cells in classical Hodgkin lymphoma (HL) often overexpress PD-1 ligands, which “strongly suggests” that HL is PD-1 dependent, the researchers noted (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

The researchers analyzed data for one group of patients within a phase Ib study of pembrolizumab in hematologic malignancies (KEYNOTE-013; NCT01953692). These 31 adults (median age, 32 years; 58% male) all had heavily pretreated classical HL – more than half had received at least five prior lines of therapy, and all had progressed on or after brentuximab vedotin therapy. Most patients (71%) also had received autologous stem cell transplantation. All 31 patients in the study received intravenous pembrolizumab (10 mg/kg) every other week.

Rates of progression-free survival were 69% at 24 weeks and 46% at 52 weeks, the researchers said. “Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways,” they reported. Those findings indicate that PD-1 blockade activates T-cell and IFN-gamma signaling pathways, which provides “a compelling rationale for the further development of PD-1 blockade in HL,” they concluded.

The most common treatment-related adverse effects were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Five patients (16%) developed grade 3 treatment-related adverse events, including elevated hepatic transaminases, axillary pain, back pain, joint swelling, colitis, and nephrotic syndrome. Two patients stopped treatment because of adverse effects, but there were no grade 4 events or deaths related to treatment, and no treatment-induced cases of hepatitis, hypophysitis, or uveitis, the researchers noted.

Merck, maker of pembrolizumab, funded the study. Dr. Armand reported financial ties to Merck, Bristol-Myers Squibb, Infinity Pharmaceuticals, Sequenta, Tensha Therapeutics, and Sigma-Tau. Senior author Craig Moskowitz, MD, and five coinvestigators disclosed consulting or advisory relationships or employment with Merck.

PD-1 checkpoint blockade via pembrolizumab is a potential option for classical Hodgkin’s lymphoma that progressed despite brentuximab vedotin therapy, based on a phase Ib, single-arm, open-label, industry-sponsored study of 31 patients.

After a median follow-up of 17 months, five (16%) patients achieved complete remission (90% confidence interval, 7%-31%), and 15 (48%) patients achieved partial remission (90% CI, 33%-64%), for an overall response rate of 65% (48%-79%). Furthermore, 70% of responses lasted at least 24 weeks, reported Philippe Armand, MD, of Dana-Farber Cancer Institute, Boston, and his associates.

“Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies,” they added. “Yet partial responses can be durable, suggesting that the achievement of complete response with checkpoint blockade is not necessary to derive significant clinical benefit.”

Pembrolizumab (Keytruda) is a humanized, highly selective IgG4 anti-PD-1 (programmed death-1) monoclonal antibody approved in the United States for patients with unresectable or metastatic melanoma or metastatic PDL-1 expressing non–small cell lung cancer. Tumor cells in classical Hodgkin lymphoma (HL) often overexpress PD-1 ligands, which “strongly suggests” that HL is PD-1 dependent, the researchers noted (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

The researchers analyzed data for one group of patients within a phase Ib study of pembrolizumab in hematologic malignancies (KEYNOTE-013; NCT01953692). These 31 adults (median age, 32 years; 58% male) all had heavily pretreated classical HL – more than half had received at least five prior lines of therapy, and all had progressed on or after brentuximab vedotin therapy. Most patients (71%) also had received autologous stem cell transplantation. All 31 patients in the study received intravenous pembrolizumab (10 mg/kg) every other week.

Rates of progression-free survival were 69% at 24 weeks and 46% at 52 weeks, the researchers said. “Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways,” they reported. Those findings indicate that PD-1 blockade activates T-cell and IFN-gamma signaling pathways, which provides “a compelling rationale for the further development of PD-1 blockade in HL,” they concluded.

The most common treatment-related adverse effects were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Five patients (16%) developed grade 3 treatment-related adverse events, including elevated hepatic transaminases, axillary pain, back pain, joint swelling, colitis, and nephrotic syndrome. Two patients stopped treatment because of adverse effects, but there were no grade 4 events or deaths related to treatment, and no treatment-induced cases of hepatitis, hypophysitis, or uveitis, the researchers noted.

Merck, maker of pembrolizumab, funded the study. Dr. Armand reported financial ties to Merck, Bristol-Myers Squibb, Infinity Pharmaceuticals, Sequenta, Tensha Therapeutics, and Sigma-Tau. Senior author Craig Moskowitz, MD, and five coinvestigators disclosed consulting or advisory relationships or employment with Merck.

PD-1 checkpoint blockade via pembrolizumab is a potential option for classical Hodgkin’s lymphoma that progressed despite brentuximab vedotin therapy, based on a phase Ib, single-arm, open-label, industry-sponsored study of 31 patients.

After a median follow-up of 17 months, five (16%) patients achieved complete remission (90% confidence interval, 7%-31%), and 15 (48%) patients achieved partial remission (90% CI, 33%-64%), for an overall response rate of 65% (48%-79%). Furthermore, 70% of responses lasted at least 24 weeks, reported Philippe Armand, MD, of Dana-Farber Cancer Institute, Boston, and his associates.

“Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies,” they added. “Yet partial responses can be durable, suggesting that the achievement of complete response with checkpoint blockade is not necessary to derive significant clinical benefit.”

Pembrolizumab (Keytruda) is a humanized, highly selective IgG4 anti-PD-1 (programmed death-1) monoclonal antibody approved in the United States for patients with unresectable or metastatic melanoma or metastatic PDL-1 expressing non–small cell lung cancer. Tumor cells in classical Hodgkin lymphoma (HL) often overexpress PD-1 ligands, which “strongly suggests” that HL is PD-1 dependent, the researchers noted (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

The researchers analyzed data for one group of patients within a phase Ib study of pembrolizumab in hematologic malignancies (KEYNOTE-013; NCT01953692). These 31 adults (median age, 32 years; 58% male) all had heavily pretreated classical HL – more than half had received at least five prior lines of therapy, and all had progressed on or after brentuximab vedotin therapy. Most patients (71%) also had received autologous stem cell transplantation. All 31 patients in the study received intravenous pembrolizumab (10 mg/kg) every other week.

Rates of progression-free survival were 69% at 24 weeks and 46% at 52 weeks, the researchers said. “Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways,” they reported. Those findings indicate that PD-1 blockade activates T-cell and IFN-gamma signaling pathways, which provides “a compelling rationale for the further development of PD-1 blockade in HL,” they concluded.

The most common treatment-related adverse effects were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Five patients (16%) developed grade 3 treatment-related adverse events, including elevated hepatic transaminases, axillary pain, back pain, joint swelling, colitis, and nephrotic syndrome. Two patients stopped treatment because of adverse effects, but there were no grade 4 events or deaths related to treatment, and no treatment-induced cases of hepatitis, hypophysitis, or uveitis, the researchers noted.

Merck, maker of pembrolizumab, funded the study. Dr. Armand reported financial ties to Merck, Bristol-Myers Squibb, Infinity Pharmaceuticals, Sequenta, Tensha Therapeutics, and Sigma-Tau. Senior author Craig Moskowitz, MD, and five coinvestigators disclosed consulting or advisory relationships or employment with Merck.

Obinutuzumab and bendamustine followed by obinutuzumab maintenance therapy was superior to bendamustine monotherapy based on progression-free survival in rituximab-refractory patients with indolent non-Hodgkin lymphoma, based on a study published online in the Lancet Oncology.

After a median follow-up of 22 months in the obinutuzumab plus bendamustine group and 20 months in the bendamustine monotherapy group, progression-free survival was significantly longer with obinutuzumab plus bendamustine (median not reached; 95% confidence interval, 22.5 months – not estimable) than with bendamustine monotherapy (14.9 months, range, 12.8-16.6; hazard ratio, 0.55; 95% CI 0.40-0.74; P = .0001). About two-thirds of the nearly 400 patients in both study arms had grade 3-5 adverse events.

The anti-CD20 monoclonal antibody obinutuzumab is an option when patients with indolent non-Hodgkin lymphoma relapse or don’t achieve adequate disease control with rituximab-based treatment, wrote Laurie H. Sehn, MD, of the British Columbia Cancer Agency and the University of British Columbia, Vancouver, and her colleagues.

In an open-label, randomized, phase III study called GADOLIN, patients with CD20-positive indolent non-Hodgkin lymphoma were stratified by indolent non-Hodgkin lymphoma subtype, rituximab-refractory type, number of previous therapies, and geographic region.

For the study, 194 patients were assigned to obinutuzumab plus bendamustine and 202 to bendamustine monotherapy. Trial participants received six 28-day cycles with either obinutuzumab plus bendamustine (obinutuzumab 1,000 mg on days 1, 8, and 15, cycle 1; and on day 1, cycles 2-6) plus bendamustine (90 mg/m² per day on days 1 and 2, cycles 1-6) or bendamustine monotherapy (120 mg/m² per day on days 1 and 2 of all cycles). Patients in the obinutuzumab plus bendamustine group whose disease did not progress received obinutuzumab maintenance therapy of 1,000 mg once every 2 months for up to 2 years.

Grade 3-5 adverse events occurred in 68% of 194 patients in the obinutuzumab plus bendamustine group and in 62% of 198 patients in the bendamustine monotherapy group. Grade 3 or worse neutropenia affected 33% of the obinutuzumab plus bendamustine group and 26% of the bendamustine monotherapy group. Other grade 3 or worse events included thrombocytopenia in 11% and 16%, anemia in 8% and 10%, and infusion-related reactions in 11% and 6%. Serious adverse events occurred in 38% in the obinutuzumab plus bendamustine group and in 33% in the bendamustine monotherapy group. Adverse events resulted in death in 6% of patients in each group.

The study was funded by Hoffmann-La Roche. Genentech, the maker of obinutuzumab (Gazyva) in the United States, is a wholly owned member of the Roche Group. Dr. Sehn receives honoraria and is a consultant or advisor to Genentech as well as several other drug companies.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Obinutuzumab and bendamustine followed by obinutuzumab maintenance therapy was superior to bendamustine monotherapy based on progression-free survival in rituximab-refractory patients with indolent non-Hodgkin lymphoma, based on a study published online in the Lancet Oncology.

After a median follow-up of 22 months in the obinutuzumab plus bendamustine group and 20 months in the bendamustine monotherapy group, progression-free survival was significantly longer with obinutuzumab plus bendamustine (median not reached; 95% confidence interval, 22.5 months – not estimable) than with bendamustine monotherapy (14.9 months, range, 12.8-16.6; hazard ratio, 0.55; 95% CI 0.40-0.74; P = .0001). About two-thirds of the nearly 400 patients in both study arms had grade 3-5 adverse events.

The anti-CD20 monoclonal antibody obinutuzumab is an option when patients with indolent non-Hodgkin lymphoma relapse or don’t achieve adequate disease control with rituximab-based treatment, wrote Laurie H. Sehn, MD, of the British Columbia Cancer Agency and the University of British Columbia, Vancouver, and her colleagues.

In an open-label, randomized, phase III study called GADOLIN, patients with CD20-positive indolent non-Hodgkin lymphoma were stratified by indolent non-Hodgkin lymphoma subtype, rituximab-refractory type, number of previous therapies, and geographic region.

For the study, 194 patients were assigned to obinutuzumab plus bendamustine and 202 to bendamustine monotherapy. Trial participants received six 28-day cycles with either obinutuzumab plus bendamustine (obinutuzumab 1,000 mg on days 1, 8, and 15, cycle 1; and on day 1, cycles 2-6) plus bendamustine (90 mg/m² per day on days 1 and 2, cycles 1-6) or bendamustine monotherapy (120 mg/m² per day on days 1 and 2 of all cycles). Patients in the obinutuzumab plus bendamustine group whose disease did not progress received obinutuzumab maintenance therapy of 1,000 mg once every 2 months for up to 2 years.

Grade 3-5 adverse events occurred in 68% of 194 patients in the obinutuzumab plus bendamustine group and in 62% of 198 patients in the bendamustine monotherapy group. Grade 3 or worse neutropenia affected 33% of the obinutuzumab plus bendamustine group and 26% of the bendamustine monotherapy group. Other grade 3 or worse events included thrombocytopenia in 11% and 16%, anemia in 8% and 10%, and infusion-related reactions in 11% and 6%. Serious adverse events occurred in 38% in the obinutuzumab plus bendamustine group and in 33% in the bendamustine monotherapy group. Adverse events resulted in death in 6% of patients in each group.

The study was funded by Hoffmann-La Roche. Genentech, the maker of obinutuzumab (Gazyva) in the United States, is a wholly owned member of the Roche Group. Dr. Sehn receives honoraria and is a consultant or advisor to Genentech as well as several other drug companies.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Obinutuzumab and bendamustine followed by obinutuzumab maintenance therapy was superior to bendamustine monotherapy based on progression-free survival in rituximab-refractory patients with indolent non-Hodgkin lymphoma, based on a study published online in the Lancet Oncology.

After a median follow-up of 22 months in the obinutuzumab plus bendamustine group and 20 months in the bendamustine monotherapy group, progression-free survival was significantly longer with obinutuzumab plus bendamustine (median not reached; 95% confidence interval, 22.5 months – not estimable) than with bendamustine monotherapy (14.9 months, range, 12.8-16.6; hazard ratio, 0.55; 95% CI 0.40-0.74; P = .0001). About two-thirds of the nearly 400 patients in both study arms had grade 3-5 adverse events.

The anti-CD20 monoclonal antibody obinutuzumab is an option when patients with indolent non-Hodgkin lymphoma relapse or don’t achieve adequate disease control with rituximab-based treatment, wrote Laurie H. Sehn, MD, of the British Columbia Cancer Agency and the University of British Columbia, Vancouver, and her colleagues.

In an open-label, randomized, phase III study called GADOLIN, patients with CD20-positive indolent non-Hodgkin lymphoma were stratified by indolent non-Hodgkin lymphoma subtype, rituximab-refractory type, number of previous therapies, and geographic region.

For the study, 194 patients were assigned to obinutuzumab plus bendamustine and 202 to bendamustine monotherapy. Trial participants received six 28-day cycles with either obinutuzumab plus bendamustine (obinutuzumab 1,000 mg on days 1, 8, and 15, cycle 1; and on day 1, cycles 2-6) plus bendamustine (90 mg/m² per day on days 1 and 2, cycles 1-6) or bendamustine monotherapy (120 mg/m² per day on days 1 and 2 of all cycles). Patients in the obinutuzumab plus bendamustine group whose disease did not progress received obinutuzumab maintenance therapy of 1,000 mg once every 2 months for up to 2 years.

Grade 3-5 adverse events occurred in 68% of 194 patients in the obinutuzumab plus bendamustine group and in 62% of 198 patients in the bendamustine monotherapy group. Grade 3 or worse neutropenia affected 33% of the obinutuzumab plus bendamustine group and 26% of the bendamustine monotherapy group. Other grade 3 or worse events included thrombocytopenia in 11% and 16%, anemia in 8% and 10%, and infusion-related reactions in 11% and 6%. Serious adverse events occurred in 38% in the obinutuzumab plus bendamustine group and in 33% in the bendamustine monotherapy group. Adverse events resulted in death in 6% of patients in each group.

The study was funded by Hoffmann-La Roche. Genentech, the maker of obinutuzumab (Gazyva) in the United States, is a wholly owned member of the Roche Group. Dr. Sehn receives honoraria and is a consultant or advisor to Genentech as well as several other drug companies.

mdales@frontlinemedcom.com

On Twitter @maryjodales

COPENHAGEN – Nivolumab may be an effective salvage therapy option for adults with Hodgkin lymphoma whose disease has progressed despite transplant and treatment with brentuximab vedotin, investigators reported.

In a subcohort of patients from the Checkmate 205 phase II trial, 80 patients with Hodgkin lymphoma who had disease progression following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), nivolumab (Opdivo) therapy was associated with a 53% objective response rate according to independent reviewers, reported Dr. Anas Younes, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, New York.

“The PD-1 checkpoint inhibitor nivolumab is an important new treatment to address unmet needs in patients with classical Hodgkin lymphoma with progressive disease and limited treatment options, especially after autologous transplant,” he said at a briefing at the annual congress of the European Hematology Association.

Objective response rates as determined by both investigators and independent reviewers were “impressive,” and had “encouraging durability,” he added. The median duration of response at time of data cutoff was 7.8 months, and the majority of patients had ongoing responses at the time of the analysis, Dr. Younes said.

Nivolumab was recently approved by the Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed or progressed after ASCT followed by brentuximab vedotin.

In the Checkmate 205 registrational trial, 80 patients (median age 37, range 18-72 years) were assigned to receive nivolumab 3 mg/kg intravenously every 2 weeks. Patients were evaluated for response by both an independent radiologic review committee (IRRC) and investigators, using 2007 International Working Group response criteria. After a median follow-up of 8.9 months, the IRRC-rated objective response rate, the primary endpoint, was 66%, including 8.8% complete remissions (CR), and 57.5% partial remissions (PR).

Dr. Younes showed a waterfall plot indicating that nearly all patients had some degree of tumor regression, and all but one patient among the responders had tumor reductions of 50% or greater from baseline.

Among 43 patients who had had no response to brentuximab vedotin, subsequent treatment with nivolumab was associated with an IRRC-rated objective response rate of 72%. As noted, the median duration of response was 7.8 months, and the median time to response was 2.1 months.

As of the last follow-up, 33 of the 53 patients with IRRC-rated responses had retained response. The IRRC-determined 6-month progression-free survival rate was 77%, and the overall survival rate was 99%.

In all, 72 patients (90%) had a treatment-related adverse event. The most common events occurring in 15% or more of patients were fatigue, infusion-related reactions, and rash. Most of the immune-mediated adverse events were of low grade and manageable, and there were no treatment-related deaths, Dr. Younes said.

Briefing moderator Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who was not involved in the study, asked whether nivolumab can be considered as a bridge to other therapies in this population.

Dr. Younes said that the “natural progression of a single-agent therapy that has efficacy is to combine it with other active agents, or use maybe in the adjuvant or maintenance setting in certain circumstances.”

“I don’t expect single-agent nivolumab to cure our patients,” he added.

A similarly designed clinical trial, MK-3457-087/KEYNOTE-087, is exploring the use of pembrolizumab (Keytruda). This trial is ongoing but does not have published data as yet.

Checkmate 205 is sponsored by Bristol-Myers Squibb. Dr. Younes has served as a consultant/advisor, received honoraria and/or research funding from Gilead Sciences, Curis, Incyte, Janssen, Seattle Genetics, Novartis, Celgene, Millennium, and Sanofi. Dr. Hagenbeek reported no relevant disclosures.

COPENHAGEN – Nivolumab may be an effective salvage therapy option for adults with Hodgkin lymphoma whose disease has progressed despite transplant and treatment with brentuximab vedotin, investigators reported.

In a subcohort of patients from the Checkmate 205 phase II trial, 80 patients with Hodgkin lymphoma who had disease progression following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), nivolumab (Opdivo) therapy was associated with a 53% objective response rate according to independent reviewers, reported Dr. Anas Younes, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, New York.

“The PD-1 checkpoint inhibitor nivolumab is an important new treatment to address unmet needs in patients with classical Hodgkin lymphoma with progressive disease and limited treatment options, especially after autologous transplant,” he said at a briefing at the annual congress of the European Hematology Association.

Objective response rates as determined by both investigators and independent reviewers were “impressive,” and had “encouraging durability,” he added. The median duration of response at time of data cutoff was 7.8 months, and the majority of patients had ongoing responses at the time of the analysis, Dr. Younes said.

Nivolumab was recently approved by the Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed or progressed after ASCT followed by brentuximab vedotin.

In the Checkmate 205 registrational trial, 80 patients (median age 37, range 18-72 years) were assigned to receive nivolumab 3 mg/kg intravenously every 2 weeks. Patients were evaluated for response by both an independent radiologic review committee (IRRC) and investigators, using 2007 International Working Group response criteria. After a median follow-up of 8.9 months, the IRRC-rated objective response rate, the primary endpoint, was 66%, including 8.8% complete remissions (CR), and 57.5% partial remissions (PR).

Dr. Younes showed a waterfall plot indicating that nearly all patients had some degree of tumor regression, and all but one patient among the responders had tumor reductions of 50% or greater from baseline.

Among 43 patients who had had no response to brentuximab vedotin, subsequent treatment with nivolumab was associated with an IRRC-rated objective response rate of 72%. As noted, the median duration of response was 7.8 months, and the median time to response was 2.1 months.

As of the last follow-up, 33 of the 53 patients with IRRC-rated responses had retained response. The IRRC-determined 6-month progression-free survival rate was 77%, and the overall survival rate was 99%.

In all, 72 patients (90%) had a treatment-related adverse event. The most common events occurring in 15% or more of patients were fatigue, infusion-related reactions, and rash. Most of the immune-mediated adverse events were of low grade and manageable, and there were no treatment-related deaths, Dr. Younes said.

Briefing moderator Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who was not involved in the study, asked whether nivolumab can be considered as a bridge to other therapies in this population.

Dr. Younes said that the “natural progression of a single-agent therapy that has efficacy is to combine it with other active agents, or use maybe in the adjuvant or maintenance setting in certain circumstances.”

“I don’t expect single-agent nivolumab to cure our patients,” he added.

A similarly designed clinical trial, MK-3457-087/KEYNOTE-087, is exploring the use of pembrolizumab (Keytruda). This trial is ongoing but does not have published data as yet.

Checkmate 205 is sponsored by Bristol-Myers Squibb. Dr. Younes has served as a consultant/advisor, received honoraria and/or research funding from Gilead Sciences, Curis, Incyte, Janssen, Seattle Genetics, Novartis, Celgene, Millennium, and Sanofi. Dr. Hagenbeek reported no relevant disclosures.

COPENHAGEN – Nivolumab may be an effective salvage therapy option for adults with Hodgkin lymphoma whose disease has progressed despite transplant and treatment with brentuximab vedotin, investigators reported.

In a subcohort of patients from the Checkmate 205 phase II trial, 80 patients with Hodgkin lymphoma who had disease progression following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), nivolumab (Opdivo) therapy was associated with a 53% objective response rate according to independent reviewers, reported Dr. Anas Younes, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, New York.

“The PD-1 checkpoint inhibitor nivolumab is an important new treatment to address unmet needs in patients with classical Hodgkin lymphoma with progressive disease and limited treatment options, especially after autologous transplant,” he said at a briefing at the annual congress of the European Hematology Association.

Objective response rates as determined by both investigators and independent reviewers were “impressive,” and had “encouraging durability,” he added. The median duration of response at time of data cutoff was 7.8 months, and the majority of patients had ongoing responses at the time of the analysis, Dr. Younes said.

Nivolumab was recently approved by the Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed or progressed after ASCT followed by brentuximab vedotin.

In the Checkmate 205 registrational trial, 80 patients (median age 37, range 18-72 years) were assigned to receive nivolumab 3 mg/kg intravenously every 2 weeks. Patients were evaluated for response by both an independent radiologic review committee (IRRC) and investigators, using 2007 International Working Group response criteria. After a median follow-up of 8.9 months, the IRRC-rated objective response rate, the primary endpoint, was 66%, including 8.8% complete remissions (CR), and 57.5% partial remissions (PR).

Dr. Younes showed a waterfall plot indicating that nearly all patients had some degree of tumor regression, and all but one patient among the responders had tumor reductions of 50% or greater from baseline.

Among 43 patients who had had no response to brentuximab vedotin, subsequent treatment with nivolumab was associated with an IRRC-rated objective response rate of 72%. As noted, the median duration of response was 7.8 months, and the median time to response was 2.1 months.

As of the last follow-up, 33 of the 53 patients with IRRC-rated responses had retained response. The IRRC-determined 6-month progression-free survival rate was 77%, and the overall survival rate was 99%.

In all, 72 patients (90%) had a treatment-related adverse event. The most common events occurring in 15% or more of patients were fatigue, infusion-related reactions, and rash. Most of the immune-mediated adverse events were of low grade and manageable, and there were no treatment-related deaths, Dr. Younes said.

Briefing moderator Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who was not involved in the study, asked whether nivolumab can be considered as a bridge to other therapies in this population.

Dr. Younes said that the “natural progression of a single-agent therapy that has efficacy is to combine it with other active agents, or use maybe in the adjuvant or maintenance setting in certain circumstances.”

“I don’t expect single-agent nivolumab to cure our patients,” he added.

A similarly designed clinical trial, MK-3457-087/KEYNOTE-087, is exploring the use of pembrolizumab (Keytruda). This trial is ongoing but does not have published data as yet.

Checkmate 205 is sponsored by Bristol-Myers Squibb. Dr. Younes has served as a consultant/advisor, received honoraria and/or research funding from Gilead Sciences, Curis, Incyte, Janssen, Seattle Genetics, Novartis, Celgene, Millennium, and Sanofi. Dr. Hagenbeek reported no relevant disclosures.

COPENHAGEN – In a classic case of clinical sibling rivalry, results of the POLLUX trial support the benefits of adding daratumumab to lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma, echoing results reported a few days earlier by investigators in the twin (and archly named) CASTOR trial

Among 569 patients with relapsed/refractory multiple myeloma, the addition of the anti-CD38 monoclonal antibody daratumumab (Darzalex) to lenalidomide (Revlimid) and dexamethasone was associated with a 63% reduction in the risk of disease progress or death, compared with len-dex alone, reported Dr. Meletios A Dimopoulos of the National and Kapodistrian University of Athens.

With daratumumab and len-dex, “there is the highest-ever response rate seen in relapsed or refractory myeloma; 93% of the patients achieved at least a partial response, and more importantly, 43% of the patients achieved a complete response,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

“The addition of daratumumab to lenalidomide and dexamethasone induces deep and durable responses. Data indicate that we can achieve minimal residual disease negativity status in a significant number of patients,” he added.

The trial was halted on May 20, 2016, after a preplanned interim analysis showed a significant improvement in the primary endpoint of a progression-free survival, compared with len-dex alone.

Dizygotic twins

Like their mythologic namesakes, who were twin sons from different fathers, the CASTOR and POLLUX trials differed somewhat in the patient populations treated and in trial design. The CASTOR trial is looking at the addition of daratumumab to bortezomib (Velcade) and dexamethasone, and excludes patients resistant to bortezomib. The POLLUX trial includes bortezomib-resistant patients, but excludes lenalidomide-resistant patients.

In addition, in CASTOR, patients were treated with the assigned regimen for a specified number of courses, followed by daratumumab maintenance, whereas patients in both arms in POLLUX continued on their assigned therapy until disease progression or unacceptable toxicity occurred.

POLLUX was a multicenter, randomized, open-label phase III trial in patients with relapsed/refractory multiple myeloma following one or more prior lines of therapy. They were randomized on a 1:1 basis to either len-dex (283 patients) or len-dex plus intravenous daratumumab at a dose of 16 mg/kg once a week during treatment cycles 1 and 2, every 2 weeks during cycles 3-6, and once only on day 1 of subsequent cycles.

After a median follow-up of 13.5 months, the median progression-free survival for patients treated with len-dex alone was 18.4 months, but the median was not yet reached among patients treated with daratumumab. The difference translated into a hazard ratio for progression-free survival with daratumumab of 0.37 (P less than .0001).

In addition, the antibody was associated with a significantly better overall response rate (93% for daratumumab vs. 76% for len-dex only; P less than .0001), as well as better rates of complete responses (43% vs. 19%, respectively; P less than .0001), and very good partial responses or better (76% vs. 44%, P less than .0001).

The combination was generally well tolerated, with adverse events consistent with the known safety profile of len-dex. Infusion reactions with daratumumab were generally mild, and tended to occur during the first infusion, Dr. Dimopoulos said.

Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam (the Netherlands), who moderated the briefing, commented that the progression-free survival curves with daratumumab appeared to plateau, and asked whether any patients in the trial could be considered to have been “cured.”

Dr. Dimopoulos replied that “although we believe that in the relapsed setting of myeloma, it is unlikely to achieve the cure rate, we are optimistic that there will be a sizable number of patients that will remain without progression for many months. Already from single-agent daratumumab where this patient population is far more heavily pretreated, there are patients who are without progression for several years.”

Dr. Dimopoulos has previously disclosed honoraria from Janssen, maker of daratumumab. Dr. Hagenbeek disclosed serving on an advisory board for Takeda, maker of bortezomib.

COPENHAGEN – In a classic case of clinical sibling rivalry, results of the POLLUX trial support the benefits of adding daratumumab to lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma, echoing results reported a few days earlier by investigators in the twin (and archly named) CASTOR trial

Among 569 patients with relapsed/refractory multiple myeloma, the addition of the anti-CD38 monoclonal antibody daratumumab (Darzalex) to lenalidomide (Revlimid) and dexamethasone was associated with a 63% reduction in the risk of disease progress or death, compared with len-dex alone, reported Dr. Meletios A Dimopoulos of the National and Kapodistrian University of Athens.

With daratumumab and len-dex, “there is the highest-ever response rate seen in relapsed or refractory myeloma; 93% of the patients achieved at least a partial response, and more importantly, 43% of the patients achieved a complete response,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

“The addition of daratumumab to lenalidomide and dexamethasone induces deep and durable responses. Data indicate that we can achieve minimal residual disease negativity status in a significant number of patients,” he added.

The trial was halted on May 20, 2016, after a preplanned interim analysis showed a significant improvement in the primary endpoint of a progression-free survival, compared with len-dex alone.

Dizygotic twins

Like their mythologic namesakes, who were twin sons from different fathers, the CASTOR and POLLUX trials differed somewhat in the patient populations treated and in trial design. The CASTOR trial is looking at the addition of daratumumab to bortezomib (Velcade) and dexamethasone, and excludes patients resistant to bortezomib. The POLLUX trial includes bortezomib-resistant patients, but excludes lenalidomide-resistant patients.

In addition, in CASTOR, patients were treated with the assigned regimen for a specified number of courses, followed by daratumumab maintenance, whereas patients in both arms in POLLUX continued on their assigned therapy until disease progression or unacceptable toxicity occurred.

POLLUX was a multicenter, randomized, open-label phase III trial in patients with relapsed/refractory multiple myeloma following one or more prior lines of therapy. They were randomized on a 1:1 basis to either len-dex (283 patients) or len-dex plus intravenous daratumumab at a dose of 16 mg/kg once a week during treatment cycles 1 and 2, every 2 weeks during cycles 3-6, and once only on day 1 of subsequent cycles.

After a median follow-up of 13.5 months, the median progression-free survival for patients treated with len-dex alone was 18.4 months, but the median was not yet reached among patients treated with daratumumab. The difference translated into a hazard ratio for progression-free survival with daratumumab of 0.37 (P less than .0001).

In addition, the antibody was associated with a significantly better overall response rate (93% for daratumumab vs. 76% for len-dex only; P less than .0001), as well as better rates of complete responses (43% vs. 19%, respectively; P less than .0001), and very good partial responses or better (76% vs. 44%, P less than .0001).

The combination was generally well tolerated, with adverse events consistent with the known safety profile of len-dex. Infusion reactions with daratumumab were generally mild, and tended to occur during the first infusion, Dr. Dimopoulos said.

Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam (the Netherlands), who moderated the briefing, commented that the progression-free survival curves with daratumumab appeared to plateau, and asked whether any patients in the trial could be considered to have been “cured.”

Dr. Dimopoulos replied that “although we believe that in the relapsed setting of myeloma, it is unlikely to achieve the cure rate, we are optimistic that there will be a sizable number of patients that will remain without progression for many months. Already from single-agent daratumumab where this patient population is far more heavily pretreated, there are patients who are without progression for several years.”

Dr. Dimopoulos has previously disclosed honoraria from Janssen, maker of daratumumab. Dr. Hagenbeek disclosed serving on an advisory board for Takeda, maker of bortezomib.

COPENHAGEN – In a classic case of clinical sibling rivalry, results of the POLLUX trial support the benefits of adding daratumumab to lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma, echoing results reported a few days earlier by investigators in the twin (and archly named) CASTOR trial

Among 569 patients with relapsed/refractory multiple myeloma, the addition of the anti-CD38 monoclonal antibody daratumumab (Darzalex) to lenalidomide (Revlimid) and dexamethasone was associated with a 63% reduction in the risk of disease progress or death, compared with len-dex alone, reported Dr. Meletios A Dimopoulos of the National and Kapodistrian University of Athens.

With daratumumab and len-dex, “there is the highest-ever response rate seen in relapsed or refractory myeloma; 93% of the patients achieved at least a partial response, and more importantly, 43% of the patients achieved a complete response,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

“The addition of daratumumab to lenalidomide and dexamethasone induces deep and durable responses. Data indicate that we can achieve minimal residual disease negativity status in a significant number of patients,” he added.

The trial was halted on May 20, 2016, after a preplanned interim analysis showed a significant improvement in the primary endpoint of a progression-free survival, compared with len-dex alone.

Dizygotic twins

Like their mythologic namesakes, who were twin sons from different fathers, the CASTOR and POLLUX trials differed somewhat in the patient populations treated and in trial design. The CASTOR trial is looking at the addition of daratumumab to bortezomib (Velcade) and dexamethasone, and excludes patients resistant to bortezomib. The POLLUX trial includes bortezomib-resistant patients, but excludes lenalidomide-resistant patients.

In addition, in CASTOR, patients were treated with the assigned regimen for a specified number of courses, followed by daratumumab maintenance, whereas patients in both arms in POLLUX continued on their assigned therapy until disease progression or unacceptable toxicity occurred.

POLLUX was a multicenter, randomized, open-label phase III trial in patients with relapsed/refractory multiple myeloma following one or more prior lines of therapy. They were randomized on a 1:1 basis to either len-dex (283 patients) or len-dex plus intravenous daratumumab at a dose of 16 mg/kg once a week during treatment cycles 1 and 2, every 2 weeks during cycles 3-6, and once only on day 1 of subsequent cycles.

After a median follow-up of 13.5 months, the median progression-free survival for patients treated with len-dex alone was 18.4 months, but the median was not yet reached among patients treated with daratumumab. The difference translated into a hazard ratio for progression-free survival with daratumumab of 0.37 (P less than .0001).

In addition, the antibody was associated with a significantly better overall response rate (93% for daratumumab vs. 76% for len-dex only; P less than .0001), as well as better rates of complete responses (43% vs. 19%, respectively; P less than .0001), and very good partial responses or better (76% vs. 44%, P less than .0001).

The combination was generally well tolerated, with adverse events consistent with the known safety profile of len-dex. Infusion reactions with daratumumab were generally mild, and tended to occur during the first infusion, Dr. Dimopoulos said.

Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam (the Netherlands), who moderated the briefing, commented that the progression-free survival curves with daratumumab appeared to plateau, and asked whether any patients in the trial could be considered to have been “cured.”

Dr. Dimopoulos replied that “although we believe that in the relapsed setting of myeloma, it is unlikely to achieve the cure rate, we are optimistic that there will be a sizable number of patients that will remain without progression for many months. Already from single-agent daratumumab where this patient population is far more heavily pretreated, there are patients who are without progression for several years.”

Dr. Dimopoulos has previously disclosed honoraria from Janssen, maker of daratumumab. Dr. Hagenbeek disclosed serving on an advisory board for Takeda, maker of bortezomib.

Among patients with high tumor burden follicular lymphoma (FL) that responded to rituximab chemotherapy but then underwent histologic transformation, median overall survival was not reached when patients received autologous stem cell transplantation (ASCT), but was only 1.7 years otherwise, based on results of an ancillary study of a clinical trial.

In contrast, ASCT did not affect overall survival when patients progressed to untransformed FL, said Dr. Clémentine Sarkozy of Centre Hospitalier Lyon-Sud in Pierre Bénite, France, and her associates. Fully 58% of histologic transformations occurred in the first year of follow-up, highlighting “the necessity for biopsy at the first recurrence of FL,” they wrote online June 13 in the Journal of Clinical Oncology.

Histologic transformation in FL signifies progression to aggressive lymphoma. Studies of histologic transformation and subsequent overall survival in the rituximab era have been retrospective, with variable patient populations and initial management regimens, according to the investigators. Therefore, they followed 1,018 patients from the multicenter, randomized, phase III PRIMA (Primary Rituximab and Maintenance) trial, which evaluated maintenance rituximab therapy among patients with symptomatic FL who had responded to induction chemotherapy plus rituximab (J Clin Oncol. 2016 Jun. doi: 10.1200/JCO.2015.65.7163).

A total of 463 patients (45.5%) experienced disease recurrence or progression, and 194 (42%) were biopsied over a median follow-up time of 6 years. A total of 40 (20.6%) biopsies showed histologic transformation, while 154 (79.4%) had untransformed FL. Median time to recurrence was 9.6 months for patients with histologic transformation and 22.8 months for patients with untransformed FL (P = .02). Median overall survival with histologic transformation was worse than with untransformed FL (3.8 years vs. 6.4 years; hazard ratio, 3.9; 95% confidence interval, 2.2-6.9; P = .001). Furthermore, among patients who progressed within 12 months, median overall survival with histologic transformation was 2 years, compared with 6.4 years for patients with untransformed FL (P = .007).

After salvage therapy, 17 (42%) patients with histologic transformation underwent consolidation with high-dose chemotherapy and ASCT. Median overall survival for these patients was not reached, versus 1.7 years when they did not undergo ASCT. In contrast, ASCT did not improve overall survival among patients with untransformed FL. Results were similar after excluding patients with early progression and patients who were older than 65 years, the investigators reported.

Risk factors for histologic transformation in the univariate analysis included performance status, anemia, high lactate dehydrogenase level, “B” symptoms, histologic grade 3a, and high Follicular Lymphoma International Prognostic Index scores at diagnosis. However, only Eastern Cooperative Oncology Group performance status of 2 to 4 (HR, 5.6; 95% CI, 1.7-17.7), and anemia (HR, 3.7; 95% CI, 1.4-9.7) remained significant in the multivariate analysis. Neither the choice of induction regimen nor the quality of response seemed to affect the likelihood of histologic transformation, and rituximab maintenance therapy did not seem to alter response to salvage treatment or survival after histologic transformation. By necessity, the study excluded patients who did not respond to initial immunochemotherapy, which could have limited the generalizability of the findings, the investigators noted.

The study was funded by Sandoz and Takeda Pharmaceuticals. Dr. Sarkozy disclosed research funding from Sandoz and Takeda Pharmaceuticals and honoraria from Gilead Sciences. Twelve coinvestigators also disclosed ties to Takeda and a number of other pharmaceutical companies. The other seven coinvestigators had no disclosures.

Among patients with high tumor burden follicular lymphoma (FL) that responded to rituximab chemotherapy but then underwent histologic transformation, median overall survival was not reached when patients received autologous stem cell transplantation (ASCT), but was only 1.7 years otherwise, based on results of an ancillary study of a clinical trial.

In contrast, ASCT did not affect overall survival when patients progressed to untransformed FL, said Dr. Clémentine Sarkozy of Centre Hospitalier Lyon-Sud in Pierre Bénite, France, and her associates. Fully 58% of histologic transformations occurred in the first year of follow-up, highlighting “the necessity for biopsy at the first recurrence of FL,” they wrote online June 13 in the Journal of Clinical Oncology.

Histologic transformation in FL signifies progression to aggressive lymphoma. Studies of histologic transformation and subsequent overall survival in the rituximab era have been retrospective, with variable patient populations and initial management regimens, according to the investigators. Therefore, they followed 1,018 patients from the multicenter, randomized, phase III PRIMA (Primary Rituximab and Maintenance) trial, which evaluated maintenance rituximab therapy among patients with symptomatic FL who had responded to induction chemotherapy plus rituximab (J Clin Oncol. 2016 Jun. doi: 10.1200/JCO.2015.65.7163).

A total of 463 patients (45.5%) experienced disease recurrence or progression, and 194 (42%) were biopsied over a median follow-up time of 6 years. A total of 40 (20.6%) biopsies showed histologic transformation, while 154 (79.4%) had untransformed FL. Median time to recurrence was 9.6 months for patients with histologic transformation and 22.8 months for patients with untransformed FL (P = .02). Median overall survival with histologic transformation was worse than with untransformed FL (3.8 years vs. 6.4 years; hazard ratio, 3.9; 95% confidence interval, 2.2-6.9; P = .001). Furthermore, among patients who progressed within 12 months, median overall survival with histologic transformation was 2 years, compared with 6.4 years for patients with untransformed FL (P = .007).

After salvage therapy, 17 (42%) patients with histologic transformation underwent consolidation with high-dose chemotherapy and ASCT. Median overall survival for these patients was not reached, versus 1.7 years when they did not undergo ASCT. In contrast, ASCT did not improve overall survival among patients with untransformed FL. Results were similar after excluding patients with early progression and patients who were older than 65 years, the investigators reported.

Risk factors for histologic transformation in the univariate analysis included performance status, anemia, high lactate dehydrogenase level, “B” symptoms, histologic grade 3a, and high Follicular Lymphoma International Prognostic Index scores at diagnosis. However, only Eastern Cooperative Oncology Group performance status of 2 to 4 (HR, 5.6; 95% CI, 1.7-17.7), and anemia (HR, 3.7; 95% CI, 1.4-9.7) remained significant in the multivariate analysis. Neither the choice of induction regimen nor the quality of response seemed to affect the likelihood of histologic transformation, and rituximab maintenance therapy did not seem to alter response to salvage treatment or survival after histologic transformation. By necessity, the study excluded patients who did not respond to initial immunochemotherapy, which could have limited the generalizability of the findings, the investigators noted.

The study was funded by Sandoz and Takeda Pharmaceuticals. Dr. Sarkozy disclosed research funding from Sandoz and Takeda Pharmaceuticals and honoraria from Gilead Sciences. Twelve coinvestigators also disclosed ties to Takeda and a number of other pharmaceutical companies. The other seven coinvestigators had no disclosures.

Among patients with high tumor burden follicular lymphoma (FL) that responded to rituximab chemotherapy but then underwent histologic transformation, median overall survival was not reached when patients received autologous stem cell transplantation (ASCT), but was only 1.7 years otherwise, based on results of an ancillary study of a clinical trial.

In contrast, ASCT did not affect overall survival when patients progressed to untransformed FL, said Dr. Clémentine Sarkozy of Centre Hospitalier Lyon-Sud in Pierre Bénite, France, and her associates. Fully 58% of histologic transformations occurred in the first year of follow-up, highlighting “the necessity for biopsy at the first recurrence of FL,” they wrote online June 13 in the Journal of Clinical Oncology.

Histologic transformation in FL signifies progression to aggressive lymphoma. Studies of histologic transformation and subsequent overall survival in the rituximab era have been retrospective, with variable patient populations and initial management regimens, according to the investigators. Therefore, they followed 1,018 patients from the multicenter, randomized, phase III PRIMA (Primary Rituximab and Maintenance) trial, which evaluated maintenance rituximab therapy among patients with symptomatic FL who had responded to induction chemotherapy plus rituximab (J Clin Oncol. 2016 Jun. doi: 10.1200/JCO.2015.65.7163).

A total of 463 patients (45.5%) experienced disease recurrence or progression, and 194 (42%) were biopsied over a median follow-up time of 6 years. A total of 40 (20.6%) biopsies showed histologic transformation, while 154 (79.4%) had untransformed FL. Median time to recurrence was 9.6 months for patients with histologic transformation and 22.8 months for patients with untransformed FL (P = .02). Median overall survival with histologic transformation was worse than with untransformed FL (3.8 years vs. 6.4 years; hazard ratio, 3.9; 95% confidence interval, 2.2-6.9; P = .001). Furthermore, among patients who progressed within 12 months, median overall survival with histologic transformation was 2 years, compared with 6.4 years for patients with untransformed FL (P = .007).

After salvage therapy, 17 (42%) patients with histologic transformation underwent consolidation with high-dose chemotherapy and ASCT. Median overall survival for these patients was not reached, versus 1.7 years when they did not undergo ASCT. In contrast, ASCT did not improve overall survival among patients with untransformed FL. Results were similar after excluding patients with early progression and patients who were older than 65 years, the investigators reported.

Risk factors for histologic transformation in the univariate analysis included performance status, anemia, high lactate dehydrogenase level, “B” symptoms, histologic grade 3a, and high Follicular Lymphoma International Prognostic Index scores at diagnosis. However, only Eastern Cooperative Oncology Group performance status of 2 to 4 (HR, 5.6; 95% CI, 1.7-17.7), and anemia (HR, 3.7; 95% CI, 1.4-9.7) remained significant in the multivariate analysis. Neither the choice of induction regimen nor the quality of response seemed to affect the likelihood of histologic transformation, and rituximab maintenance therapy did not seem to alter response to salvage treatment or survival after histologic transformation. By necessity, the study excluded patients who did not respond to initial immunochemotherapy, which could have limited the generalizability of the findings, the investigators noted.

The study was funded by Sandoz and Takeda Pharmaceuticals. Dr. Sarkozy disclosed research funding from Sandoz and Takeda Pharmaceuticals and honoraria from Gilead Sciences. Twelve coinvestigators also disclosed ties to Takeda and a number of other pharmaceutical companies. The other seven coinvestigators had no disclosures.

CHICAGO – The anti-CCR4 monoclonal antibody mogamulizumab was superior to other investigator-selected therapies for the treatment of patients with relapsed/refractory adult T-cell leukemia-lymphoma (ATL), based on results from 71 patients in a prospective, multicenter, randomized study reported at the annual meeting of the American Society of Clinical Oncology.

Commonly used cytotoxic regimens provided limited therapeutic benefit for these patients, but mogamulizumab resulted in an objective response rate that supports its therapeutic potential in this setting, reported Dr. Adrienne Alise Phillips of New York Presbyterian/Weill Cornell Medical College, New York.

Mary Jo Dales/Frontline Medical News

A malignancy of T-cells infected with HTLV-1, ATL has a poor prognosis with a median overall survival of less than 3 months in patients with relapsed/refractory disease. CCR4 is expressed in over 90% of ATL patients, and mogamulizumab is approved in Japan for ATL as well as for peripheral T-cell lymphoma and cutaneous T-cell lymphoma.

The 71 patients in the study were from the United States, the European Union and Latin America. The study is the largest randomized clinical trial of relapsed/refractory adult T-cell leukemia-lymphoma thus far conducted. The patients were randomized in 2:1 fashion 47:24 patients) to mogamulizumab, 1.0 mg/kg, given weekly for the first 4-week cycle and then biweekly, or to one of three investigator choice regimens [gemcitabine and oxaliplatin, DHAP (dexamethasone, high-dose cytarabine, and cisplatin), or pralatrexate]. Patients who were in the investigator-choice arm and whose disease progressed were permitted to cross over to mogamulizumab.

The primary endpoint was objective response rate based on modified Tsukasaki criteria and assessed by the treating investigator and in blinded fashion by independent review.

The objective response rate in the mogamulizumab-treated group was 23.4% (11 of 47) by independent review and 34% (16 of 47) by the treating investigator. In the investigator choice group, the overall response rate was 2 of 24 by independent review and 0 of 24 by the treating investigator.

The confirmed objective response rate after 1 month in the mogamulizumab-treated group was 10.6% by independent review and 14.9% by the treating investigator; there were no confirmed responses in the investigator-choice arm. Of 18 patients who crossed over to mogamulizumab, 3 responded. The median duration of response for mogamulizumab was 5 months; one patient had a complete response that lasted over 9 months and the survival data are not yet mature.

Mogamulizumab had few drug-related adverse events, primarily infusion reactions (46.8%), rash/drug eruption (25.5%) and infections (14.9%).

Dr. Phillips disclosed ties to Celgene, Genentech, and Takeda, as well as research funding from Kyowa Hakko Kirin, the sponsor of the study.

Abstract 7501

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – The anti-CCR4 monoclonal antibody mogamulizumab was superior to other investigator-selected therapies for the treatment of patients with relapsed/refractory adult T-cell leukemia-lymphoma (ATL), based on results from 71 patients in a prospective, multicenter, randomized study reported at the annual meeting of the American Society of Clinical Oncology.

Commonly used cytotoxic regimens provided limited therapeutic benefit for these patients, but mogamulizumab resulted in an objective response rate that supports its therapeutic potential in this setting, reported Dr. Adrienne Alise Phillips of New York Presbyterian/Weill Cornell Medical College, New York.

Mary Jo Dales/Frontline Medical News

A malignancy of T-cells infected with HTLV-1, ATL has a poor prognosis with a median overall survival of less than 3 months in patients with relapsed/refractory disease. CCR4 is expressed in over 90% of ATL patients, and mogamulizumab is approved in Japan for ATL as well as for peripheral T-cell lymphoma and cutaneous T-cell lymphoma.

The 71 patients in the study were from the United States, the European Union and Latin America. The study is the largest randomized clinical trial of relapsed/refractory adult T-cell leukemia-lymphoma thus far conducted. The patients were randomized in 2:1 fashion 47:24 patients) to mogamulizumab, 1.0 mg/kg, given weekly for the first 4-week cycle and then biweekly, or to one of three investigator choice regimens [gemcitabine and oxaliplatin, DHAP (dexamethasone, high-dose cytarabine, and cisplatin), or pralatrexate]. Patients who were in the investigator-choice arm and whose disease progressed were permitted to cross over to mogamulizumab.

The primary endpoint was objective response rate based on modified Tsukasaki criteria and assessed by the treating investigator and in blinded fashion by independent review.

The objective response rate in the mogamulizumab-treated group was 23.4% (11 of 47) by independent review and 34% (16 of 47) by the treating investigator. In the investigator choice group, the overall response rate was 2 of 24 by independent review and 0 of 24 by the treating investigator.

The confirmed objective response rate after 1 month in the mogamulizumab-treated group was 10.6% by independent review and 14.9% by the treating investigator; there were no confirmed responses in the investigator-choice arm. Of 18 patients who crossed over to mogamulizumab, 3 responded. The median duration of response for mogamulizumab was 5 months; one patient had a complete response that lasted over 9 months and the survival data are not yet mature.

Mogamulizumab had few drug-related adverse events, primarily infusion reactions (46.8%), rash/drug eruption (25.5%) and infections (14.9%).

Dr. Phillips disclosed ties to Celgene, Genentech, and Takeda, as well as research funding from Kyowa Hakko Kirin, the sponsor of the study.

Abstract 7501

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – The anti-CCR4 monoclonal antibody mogamulizumab was superior to other investigator-selected therapies for the treatment of patients with relapsed/refractory adult T-cell leukemia-lymphoma (ATL), based on results from 71 patients in a prospective, multicenter, randomized study reported at the annual meeting of the American Society of Clinical Oncology.

Commonly used cytotoxic regimens provided limited therapeutic benefit for these patients, but mogamulizumab resulted in an objective response rate that supports its therapeutic potential in this setting, reported Dr. Adrienne Alise Phillips of New York Presbyterian/Weill Cornell Medical College, New York.

Mary Jo Dales/Frontline Medical News

A malignancy of T-cells infected with HTLV-1, ATL has a poor prognosis with a median overall survival of less than 3 months in patients with relapsed/refractory disease. CCR4 is expressed in over 90% of ATL patients, and mogamulizumab is approved in Japan for ATL as well as for peripheral T-cell lymphoma and cutaneous T-cell lymphoma.

The 71 patients in the study were from the United States, the European Union and Latin America. The study is the largest randomized clinical trial of relapsed/refractory adult T-cell leukemia-lymphoma thus far conducted. The patients were randomized in 2:1 fashion 47:24 patients) to mogamulizumab, 1.0 mg/kg, given weekly for the first 4-week cycle and then biweekly, or to one of three investigator choice regimens [gemcitabine and oxaliplatin, DHAP (dexamethasone, high-dose cytarabine, and cisplatin), or pralatrexate]. Patients who were in the investigator-choice arm and whose disease progressed were permitted to cross over to mogamulizumab.

The primary endpoint was objective response rate based on modified Tsukasaki criteria and assessed by the treating investigator and in blinded fashion by independent review.

The objective response rate in the mogamulizumab-treated group was 23.4% (11 of 47) by independent review and 34% (16 of 47) by the treating investigator. In the investigator choice group, the overall response rate was 2 of 24 by independent review and 0 of 24 by the treating investigator.

The confirmed objective response rate after 1 month in the mogamulizumab-treated group was 10.6% by independent review and 14.9% by the treating investigator; there were no confirmed responses in the investigator-choice arm. Of 18 patients who crossed over to mogamulizumab, 3 responded. The median duration of response for mogamulizumab was 5 months; one patient had a complete response that lasted over 9 months and the survival data are not yet mature.

Mogamulizumab had few drug-related adverse events, primarily infusion reactions (46.8%), rash/drug eruption (25.5%) and infections (14.9%).

Dr. Phillips disclosed ties to Celgene, Genentech, and Takeda, as well as research funding from Kyowa Hakko Kirin, the sponsor of the study.

Abstract 7501

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – Adding the monoclonal anti-CD52 antibody alemtuzumab to CHOP (A-CHOP) increased response rates in elderly patients with peripheral T-cell lymphomas but did not improve their survival, based on the final results from 116 patients treated in the international ACT-2 phase III trial.

Complete responses were seen in 43% of 58 patients given CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and in 60% of 58 patients given A-CHOP in the trial. However, trial participants did not significantly differ in event-free survival and progression-free survival at 3 years.

Further, overall survival at 3 years was 38% for the patients given A-CHOP and 56% for the patients given CHOP. The poorer overall survival was mainly the result of treatment-related toxicity, Dr. Lorenz H. Trümper reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 3-year disease-free survival is 25% for elderly patients with peripheral T-cell lymphomas. Previous phase II trials had indicated that alemtuzumab was active in primary and relapsed T-cell lymphoma, prompting the study of adjuvant alemtuzumab in combination with dose-dense CHOP-14 in patients with previously untreated peripheral T-cell lymphoma, he said.

Although the treatment protocol demanded stringent monitoring for cytomegalovirus and Epstein-Barr virus and anti-infective prophylaxis, there were more grade 3 or higher infections in the A-CHOP group (40%) than the CHOP group (21%). The higher infection rates were attributed to higher rates of grade 3/4 hematotoxicity in patients given A-CHOP. Grade 4 leukocytopenia was seen in 70% with A-CHOP and 54% with CHOP; grade 3/4 thrombocytopenia was seen in 19% given A-CHOP and 13% given CHOP, according to Dr. Trümper of the University of Göttingen, Germany.

For the study, 116 patients from 52 centers were randomized to receive either six cycles of CHOP or A-CHOP given at 14-day intervals with granulocyte-colony stimulating factor (G-CSF) support. Initially, patients received a total of 360 mg of alemtuzumab (90 mg given at each of the first four cycles of CHOP). After patient 39 was enrolled, the dose was reduced to 120 mg (30 mg given at each of the first four cycles of CHOP). Median patient age was 69 years, and 58% of the trial participants were men.

Treatment was completed as planned in 79% of the CHOP patients and in 57% of the A-CHOP patients.

The study was sponsored by the University of Göttingen. Dr. Trümper is a consultant or adviser to Hexal and Janssen-Ortho, and receives research funding from Genzyme, the maker of alemtuzumab (Lemtrada), as well as other drug companies.

Abstract 7500

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – Adding the monoclonal anti-CD52 antibody alemtuzumab to CHOP (A-CHOP) increased response rates in elderly patients with peripheral T-cell lymphomas but did not improve their survival, based on the final results from 116 patients treated in the international ACT-2 phase III trial.

Complete responses were seen in 43% of 58 patients given CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and in 60% of 58 patients given A-CHOP in the trial. However, trial participants did not significantly differ in event-free survival and progression-free survival at 3 years.

Further, overall survival at 3 years was 38% for the patients given A-CHOP and 56% for the patients given CHOP. The poorer overall survival was mainly the result of treatment-related toxicity, Dr. Lorenz H. Trümper reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 3-year disease-free survival is 25% for elderly patients with peripheral T-cell lymphomas. Previous phase II trials had indicated that alemtuzumab was active in primary and relapsed T-cell lymphoma, prompting the study of adjuvant alemtuzumab in combination with dose-dense CHOP-14 in patients with previously untreated peripheral T-cell lymphoma, he said.

Although the treatment protocol demanded stringent monitoring for cytomegalovirus and Epstein-Barr virus and anti-infective prophylaxis, there were more grade 3 or higher infections in the A-CHOP group (40%) than the CHOP group (21%). The higher infection rates were attributed to higher rates of grade 3/4 hematotoxicity in patients given A-CHOP. Grade 4 leukocytopenia was seen in 70% with A-CHOP and 54% with CHOP; grade 3/4 thrombocytopenia was seen in 19% given A-CHOP and 13% given CHOP, according to Dr. Trümper of the University of Göttingen, Germany.

For the study, 116 patients from 52 centers were randomized to receive either six cycles of CHOP or A-CHOP given at 14-day intervals with granulocyte-colony stimulating factor (G-CSF) support. Initially, patients received a total of 360 mg of alemtuzumab (90 mg given at each of the first four cycles of CHOP). After patient 39 was enrolled, the dose was reduced to 120 mg (30 mg given at each of the first four cycles of CHOP). Median patient age was 69 years, and 58% of the trial participants were men.

Treatment was completed as planned in 79% of the CHOP patients and in 57% of the A-CHOP patients.

The study was sponsored by the University of Göttingen. Dr. Trümper is a consultant or adviser to Hexal and Janssen-Ortho, and receives research funding from Genzyme, the maker of alemtuzumab (Lemtrada), as well as other drug companies.

Abstract 7500

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – Adding the monoclonal anti-CD52 antibody alemtuzumab to CHOP (A-CHOP) increased response rates in elderly patients with peripheral T-cell lymphomas but did not improve their survival, based on the final results from 116 patients treated in the international ACT-2 phase III trial.

Complete responses were seen in 43% of 58 patients given CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and in 60% of 58 patients given A-CHOP in the trial. However, trial participants did not significantly differ in event-free survival and progression-free survival at 3 years.

Further, overall survival at 3 years was 38% for the patients given A-CHOP and 56% for the patients given CHOP. The poorer overall survival was mainly the result of treatment-related toxicity, Dr. Lorenz H. Trümper reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 3-year disease-free survival is 25% for elderly patients with peripheral T-cell lymphomas. Previous phase II trials had indicated that alemtuzumab was active in primary and relapsed T-cell lymphoma, prompting the study of adjuvant alemtuzumab in combination with dose-dense CHOP-14 in patients with previously untreated peripheral T-cell lymphoma, he said.

Although the treatment protocol demanded stringent monitoring for cytomegalovirus and Epstein-Barr virus and anti-infective prophylaxis, there were more grade 3 or higher infections in the A-CHOP group (40%) than the CHOP group (21%). The higher infection rates were attributed to higher rates of grade 3/4 hematotoxicity in patients given A-CHOP. Grade 4 leukocytopenia was seen in 70% with A-CHOP and 54% with CHOP; grade 3/4 thrombocytopenia was seen in 19% given A-CHOP and 13% given CHOP, according to Dr. Trümper of the University of Göttingen, Germany.

For the study, 116 patients from 52 centers were randomized to receive either six cycles of CHOP or A-CHOP given at 14-day intervals with granulocyte-colony stimulating factor (G-CSF) support. Initially, patients received a total of 360 mg of alemtuzumab (90 mg given at each of the first four cycles of CHOP). After patient 39 was enrolled, the dose was reduced to 120 mg (30 mg given at each of the first four cycles of CHOP). Median patient age was 69 years, and 58% of the trial participants were men.

Treatment was completed as planned in 79% of the CHOP patients and in 57% of the A-CHOP patients.

The study was sponsored by the University of Göttingen. Dr. Trümper is a consultant or adviser to Hexal and Janssen-Ortho, and receives research funding from Genzyme, the maker of alemtuzumab (Lemtrada), as well as other drug companies.

Abstract 7500

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – Brentuximab vedotin appears to be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage non-bulky Hodgkin lymphoma, Dr. Steven I. Park reported at the annual meeting of the American Society of Clinical Oncology.

After two cycles of ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine], 72% of 40 evaluable patients achieved PET-negative disease. After completing brentuximab vedotin therapy, 90% of patients had PET-negative disease. With a median follow-up of 12 months, the estimated 1-year progression-free survival rate is 91%, and the overall survival rate is 96%.

The current standard therapy for limited stage Hodgkin lymphoma is about 4-6 cycles of chemotherapy with or without consolidative radiation therapy. The goal of the study was to reduce the number of cycles of chemotherapy and avoid radiation therapy, which has an unclear overall survival advantage and risks long-term side effects, noted Dr. Park of the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center.

In this phase II multicenter study, 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma received ABVD followed by brentuximab vedotin (NCT01578967). Study patients’ median age was 29 years (range 19-67), and 46% presented with unfavorable disease. Over 90% of patients received four or fewer cycles of ABVD, and one patient received radiation due to disease progression.

Grade 3 or higher toxicities associated with brentuximab vedotin included neutropenia in three patients and peripheral neuropathy and rash in one patient each. One patient developed pancreatitis and died due to sepsis and hepatic failure, a rare complication of brentuximab vedotin that cautions regarding its use in patients with hepatic function limitations, Dr. Park said.

According to Seattle Genetics, the maker of brentuximab vedotin, the drug is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to the cytotoxic agent monomethyl auristatin E, which leads to target cell death when internalized into CD30-expressing tumor cells.

Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – Brentuximab vedotin appears to be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage non-bulky Hodgkin lymphoma, Dr. Steven I. Park reported at the annual meeting of the American Society of Clinical Oncology.

After two cycles of ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine], 72% of 40 evaluable patients achieved PET-negative disease. After completing brentuximab vedotin therapy, 90% of patients had PET-negative disease. With a median follow-up of 12 months, the estimated 1-year progression-free survival rate is 91%, and the overall survival rate is 96%.

The current standard therapy for limited stage Hodgkin lymphoma is about 4-6 cycles of chemotherapy with or without consolidative radiation therapy. The goal of the study was to reduce the number of cycles of chemotherapy and avoid radiation therapy, which has an unclear overall survival advantage and risks long-term side effects, noted Dr. Park of the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center.

In this phase II multicenter study, 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma received ABVD followed by brentuximab vedotin (NCT01578967). Study patients’ median age was 29 years (range 19-67), and 46% presented with unfavorable disease. Over 90% of patients received four or fewer cycles of ABVD, and one patient received radiation due to disease progression.

Grade 3 or higher toxicities associated with brentuximab vedotin included neutropenia in three patients and peripheral neuropathy and rash in one patient each. One patient developed pancreatitis and died due to sepsis and hepatic failure, a rare complication of brentuximab vedotin that cautions regarding its use in patients with hepatic function limitations, Dr. Park said.

According to Seattle Genetics, the maker of brentuximab vedotin, the drug is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to the cytotoxic agent monomethyl auristatin E, which leads to target cell death when internalized into CD30-expressing tumor cells.

Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – Brentuximab vedotin appears to be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage non-bulky Hodgkin lymphoma, Dr. Steven I. Park reported at the annual meeting of the American Society of Clinical Oncology.

After two cycles of ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine], 72% of 40 evaluable patients achieved PET-negative disease. After completing brentuximab vedotin therapy, 90% of patients had PET-negative disease. With a median follow-up of 12 months, the estimated 1-year progression-free survival rate is 91%, and the overall survival rate is 96%.

The current standard therapy for limited stage Hodgkin lymphoma is about 4-6 cycles of chemotherapy with or without consolidative radiation therapy. The goal of the study was to reduce the number of cycles of chemotherapy and avoid radiation therapy, which has an unclear overall survival advantage and risks long-term side effects, noted Dr. Park of the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center.

In this phase II multicenter study, 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma received ABVD followed by brentuximab vedotin (NCT01578967). Study patients’ median age was 29 years (range 19-67), and 46% presented with unfavorable disease. Over 90% of patients received four or fewer cycles of ABVD, and one patient received radiation due to disease progression.

Grade 3 or higher toxicities associated with brentuximab vedotin included neutropenia in three patients and peripheral neuropathy and rash in one patient each. One patient developed pancreatitis and died due to sepsis and hepatic failure, a rare complication of brentuximab vedotin that cautions regarding its use in patients with hepatic function limitations, Dr. Park said.

According to Seattle Genetics, the maker of brentuximab vedotin, the drug is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to the cytotoxic agent monomethyl auristatin E, which leads to target cell death when internalized into CD30-expressing tumor cells.

Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Maintenance therapy with enzastaurin, an experimental agent directed against B-cell malignancies, did not improve disease-free survival among patients with high-risk diffuse large B-cell lymphomas following complete responses to chemotherapy with rituximab.

In a randomized, double-blind trial, after a median follow-up of 48 months, the hazard ratio for disease-free survival with enzastaurin vs. placebo, the primary endpoint, was 0.92 (P = .541), reported Dr. Michael Crump of Princess Margaret Cancer Centre in Toronto, and colleagues.

WikimediaCommons/Copyright © 2011 Michael Bonert.

“The risk of treatment failure, however defined, is likely to be different in the subpopulation of patients who achieve remission after that treatment. Furthermore, identifying the value of specific biomarkers in predicting therapeutic response to novel targeted agents may be necessary in guiding future trials within defined subgroups of patients with DLBCL,” they wrote in the study, published online May 23 in Journal of Clinical Oncology.

Enzastaurin is a selective inhibitor of the protein kinase C-beta isoform (PKC-beta) expressed in both normal and malignant B cells. It has been shown to decrease tumor proliferation and induced apoptosis in cancer cells, and has been shown to have activity against relapsed or refractory DLBCL, mantle cell lymphoma, and follicular lymphoma, the authors explained.

Dr. Crump and colleagues conducted a phase III study to determine whether enzastaurin could be effective as maintenance therapy in patients with DLBCL at high risk for relapse after having had complete responses to first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

They enrolled 758 patients with stage II bulky DLBCL or stage III-IV disease who had three or more International Prognostic Index risk factors at diagnosis, and who had achieved either a confirmed or unconfirmed complete response after six to eight cycles of R-CHOP.

The patients were randomly assigned on a 2:1 basis to receive either oral enzastaurin 500 mg daily or placebo for 3 years, or until disease progression or unacceptable toxicity,

As noted, there was no significant difference in DFS with the active drug vs. placebo. In addition, in correlative analyses looking for biomarkers of response by cell of origin (i.e., germinal-center or non–germinal-center B cell) or by PKC-beta protein expression, the authors found no significant associations with either DFS or overall survival.

Enzastaurin was generally safe, with minor and manageable adverse events. More patients in the enzastaurin arm had episodes of QTc prolongation, but these did not require discontinuation of the drug.

Dr. Crump and coauthors disclosed consulting, advising, research funding and other relationships with various companies, including Eli Lilly. Five coauthors are Lilly employees.

Maintenance therapy with enzastaurin, an experimental agent directed against B-cell malignancies, did not improve disease-free survival among patients with high-risk diffuse large B-cell lymphomas following complete responses to chemotherapy with rituximab.

In a randomized, double-blind trial, after a median follow-up of 48 months, the hazard ratio for disease-free survival with enzastaurin vs. placebo, the primary endpoint, was 0.92 (P = .541), reported Dr. Michael Crump of Princess Margaret Cancer Centre in Toronto, and colleagues.

WikimediaCommons/Copyright © 2011 Michael Bonert.

“The risk of treatment failure, however defined, is likely to be different in the subpopulation of patients who achieve remission after that treatment. Furthermore, identifying the value of specific biomarkers in predicting therapeutic response to novel targeted agents may be necessary in guiding future trials within defined subgroups of patients with DLBCL,” they wrote in the study, published online May 23 in Journal of Clinical Oncology.

Enzastaurin is a selective inhibitor of the protein kinase C-beta isoform (PKC-beta) expressed in both normal and malignant B cells. It has been shown to decrease tumor proliferation and induced apoptosis in cancer cells, and has been shown to have activity against relapsed or refractory DLBCL, mantle cell lymphoma, and follicular lymphoma, the authors explained.

Dr. Crump and colleagues conducted a phase III study to determine whether enzastaurin could be effective as maintenance therapy in patients with DLBCL at high risk for relapse after having had complete responses to first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

They enrolled 758 patients with stage II bulky DLBCL or stage III-IV disease who had three or more International Prognostic Index risk factors at diagnosis, and who had achieved either a confirmed or unconfirmed complete response after six to eight cycles of R-CHOP.

The patients were randomly assigned on a 2:1 basis to receive either oral enzastaurin 500 mg daily or placebo for 3 years, or until disease progression or unacceptable toxicity,

As noted, there was no significant difference in DFS with the active drug vs. placebo. In addition, in correlative analyses looking for biomarkers of response by cell of origin (i.e., germinal-center or non–germinal-center B cell) or by PKC-beta protein expression, the authors found no significant associations with either DFS or overall survival.

Enzastaurin was generally safe, with minor and manageable adverse events. More patients in the enzastaurin arm had episodes of QTc prolongation, but these did not require discontinuation of the drug.

Dr. Crump and coauthors disclosed consulting, advising, research funding and other relationships with various companies, including Eli Lilly. Five coauthors are Lilly employees.

Maintenance therapy with enzastaurin, an experimental agent directed against B-cell malignancies, did not improve disease-free survival among patients with high-risk diffuse large B-cell lymphomas following complete responses to chemotherapy with rituximab.

In a randomized, double-blind trial, after a median follow-up of 48 months, the hazard ratio for disease-free survival with enzastaurin vs. placebo, the primary endpoint, was 0.92 (P = .541), reported Dr. Michael Crump of Princess Margaret Cancer Centre in Toronto, and colleagues.

WikimediaCommons/Copyright © 2011 Michael Bonert.

“The risk of treatment failure, however defined, is likely to be different in the subpopulation of patients who achieve remission after that treatment. Furthermore, identifying the value of specific biomarkers in predicting therapeutic response to novel targeted agents may be necessary in guiding future trials within defined subgroups of patients with DLBCL,” they wrote in the study, published online May 23 in Journal of Clinical Oncology.

Enzastaurin is a selective inhibitor of the protein kinase C-beta isoform (PKC-beta) expressed in both normal and malignant B cells. It has been shown to decrease tumor proliferation and induced apoptosis in cancer cells, and has been shown to have activity against relapsed or refractory DLBCL, mantle cell lymphoma, and follicular lymphoma, the authors explained.

Dr. Crump and colleagues conducted a phase III study to determine whether enzastaurin could be effective as maintenance therapy in patients with DLBCL at high risk for relapse after having had complete responses to first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

They enrolled 758 patients with stage II bulky DLBCL or stage III-IV disease who had three or more International Prognostic Index risk factors at diagnosis, and who had achieved either a confirmed or unconfirmed complete response after six to eight cycles of R-CHOP.

The patients were randomly assigned on a 2:1 basis to receive either oral enzastaurin 500 mg daily or placebo for 3 years, or until disease progression or unacceptable toxicity,

As noted, there was no significant difference in DFS with the active drug vs. placebo. In addition, in correlative analyses looking for biomarkers of response by cell of origin (i.e., germinal-center or non–germinal-center B cell) or by PKC-beta protein expression, the authors found no significant associations with either DFS or overall survival.

Enzastaurin was generally safe, with minor and manageable adverse events. More patients in the enzastaurin arm had episodes of QTc prolongation, but these did not require discontinuation of the drug.

Dr. Crump and coauthors disclosed consulting, advising, research funding and other relationships with various companies, including Eli Lilly. Five coauthors are Lilly employees.