Drug prolongs PFS in indolent, refractory NHL

 

 

Inside McCormick Place, site of

the 2015 ASCO Annual Meeting

 

CHICAGO—Adding obinutuzumab to treatment with bendamustine improves progression-free survival (PFS) in patients with rituximab-refractory, indolent non-Hodgkin lymphoma (NHL), interim results of the phase 3 GADOLIN trial suggest.

Study investigators said patients who received obinutuzumab and bendamustine followed by obinutuzumab maintenance had roughly double the PFS of patients who received bendamustine alone.

There was no significant difference between the treatment groups with regard to response rates or overall survival (OS), but the investigators said longer follow-up is needed to determine if obinutuzumab confers a benefit in OS.

This trial was stopped before its protocol-specified final analysis because of the PFS benefit observed in the obinutuzumab arm.

Laurie Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, presented these results at the 2015 ASCO Annual Meeting (abstract LBA8502). Genentech Inc. and F. Hoffmann-La Roche Ltd. funded this research.

The trial included 413 patients with rituximab-refractory NHL, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and Waldenstrom’s macroglobulinemia (WM).

The patients were randomized to receive bendamustine alone (120 mg/m²/day on days 1 and 2 for up to six 28-day cycles) or a combination of bendamustine (90 mg/m²/day on days 1 and 2 for up to six 28-day cycles) plus obinutuzumab (1000 mg on days 1, 8, and 15 for cycle 1, followed by 1 dose for up to six 28-day cycles), followed by obinutuzumab maintenance (1000 mg every 2 months for 2 years or until progression).

Dr Sehn said there were no significant differences in baseline characteristics between the treatment arms. Patients in both arms had received a median of 2 prior treatments, and the median time from last treatment was about 4 months.

Of the 194 patients randomized to treatment in the obinutuzumab-bendamustine (OB) arm, 79.9% had FL, 13.9% had MZL, and 6.2% had SLL. Of the 202 patients randomized to the bendamustine-alone (control) arm, 82.2% had FL, 9.4% had MZL, 7.9% had SLL, and 0.5% had WM.

Ultimately, 156 patients completed induction in the OB arm, as did 129 patients in the control arm. Thirty-six patients completed maintenance with obinutuzumab, and 46 were still receiving maintenance at the time of analysis.

Safety results

Dr Sehn said there were no unexpected safety signals among patients in the OB arm.

About 99% of patients in the OB arm experienced at least 1 adverse event (AE), as did 98% of patients in the control arm. Severe AEs occurred in 38.1% and 32.8% of patients, respectively, and grade 3/4 AEs occurred in 67% and 62.1%, respectively.

AEs leading to treatment withdrawal occurred in 18% and 15.7% of patients, respectively. And AEs leading to death occurred in 6.2% and 6.1%, respectively.

Grade 3/4 AEs that occurred in at least 2% of patients in the OB and control arms, respectively, were neutropenia (33% vs 26.3%), thrombocytopenia (10.8% vs 16.2%), infusion-related reactions (10.8% vs 5.6%), anemia (7.7% vs 10.1%), febrile neutropenia (4.6% vs 3.5%), nausea (1% vs 3%), fatigue (1.5% vs 2.5%), diarrhea (1% vs 2.5%), and vomiting (2.1% vs 1%).

Response and survival

According to an independent radiology facility, 69.2% of patients in the OB arm had responded to treatment at the end of induction, as had 63% of the control arm. The best overall response by the 12-month mark was 78.7% and 76.6%, respectively.

The median follow-up was 21 months. At that point, the median PFS had not been reached in the OB arm but was 14.9 months in the control arm (P<0.0001), according to the independent radiology facility.

According to investigators, the median PFS was 29.2 months and 14 months, respectively (P<0.0001).

The median OS has not been reached in either arm (P=0.4017). Thirty-four patients (18%) in the OB arm died, as did 41 (20%) in the control arm.

Dr Sehn said longer follow-up is needed to determine the potential OS benefit associated with obinutuzumab, but the PFS benefit of OB is clinically meaningful.

“The fact that this new approach doubled average remission time marks a major step forward for our patients,” she said. “Obinutuzumab may offer patients the chance to stay well for a significantly longer period of time, putting off the need for additional chemotherapy.”

 

 

Inside McCormick Place, site of

the 2015 ASCO Annual Meeting

 

CHICAGO—Adding obinutuzumab to treatment with bendamustine improves progression-free survival (PFS) in patients with rituximab-refractory, indolent non-Hodgkin lymphoma (NHL), interim results of the phase 3 GADOLIN trial suggest.

Study investigators said patients who received obinutuzumab and bendamustine followed by obinutuzumab maintenance had roughly double the PFS of patients who received bendamustine alone.

There was no significant difference between the treatment groups with regard to response rates or overall survival (OS), but the investigators said longer follow-up is needed to determine if obinutuzumab confers a benefit in OS.

This trial was stopped before its protocol-specified final analysis because of the PFS benefit observed in the obinutuzumab arm.

Laurie Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, presented these results at the 2015 ASCO Annual Meeting (abstract LBA8502). Genentech Inc. and F. Hoffmann-La Roche Ltd. funded this research.

The trial included 413 patients with rituximab-refractory NHL, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and Waldenstrom’s macroglobulinemia (WM).

The patients were randomized to receive bendamustine alone (120 mg/m²/day on days 1 and 2 for up to six 28-day cycles) or a combination of bendamustine (90 mg/m²/day on days 1 and 2 for up to six 28-day cycles) plus obinutuzumab (1000 mg on days 1, 8, and 15 for cycle 1, followed by 1 dose for up to six 28-day cycles), followed by obinutuzumab maintenance (1000 mg every 2 months for 2 years or until progression).

Dr Sehn said there were no significant differences in baseline characteristics between the treatment arms. Patients in both arms had received a median of 2 prior treatments, and the median time from last treatment was about 4 months.

Of the 194 patients randomized to treatment in the obinutuzumab-bendamustine (OB) arm, 79.9% had FL, 13.9% had MZL, and 6.2% had SLL. Of the 202 patients randomized to the bendamustine-alone (control) arm, 82.2% had FL, 9.4% had MZL, 7.9% had SLL, and 0.5% had WM.

Ultimately, 156 patients completed induction in the OB arm, as did 129 patients in the control arm. Thirty-six patients completed maintenance with obinutuzumab, and 46 were still receiving maintenance at the time of analysis.

Safety results

Dr Sehn said there were no unexpected safety signals among patients in the OB arm.

About 99% of patients in the OB arm experienced at least 1 adverse event (AE), as did 98% of patients in the control arm. Severe AEs occurred in 38.1% and 32.8% of patients, respectively, and grade 3/4 AEs occurred in 67% and 62.1%, respectively.

AEs leading to treatment withdrawal occurred in 18% and 15.7% of patients, respectively. And AEs leading to death occurred in 6.2% and 6.1%, respectively.

Grade 3/4 AEs that occurred in at least 2% of patients in the OB and control arms, respectively, were neutropenia (33% vs 26.3%), thrombocytopenia (10.8% vs 16.2%), infusion-related reactions (10.8% vs 5.6%), anemia (7.7% vs 10.1%), febrile neutropenia (4.6% vs 3.5%), nausea (1% vs 3%), fatigue (1.5% vs 2.5%), diarrhea (1% vs 2.5%), and vomiting (2.1% vs 1%).

Response and survival

According to an independent radiology facility, 69.2% of patients in the OB arm had responded to treatment at the end of induction, as had 63% of the control arm. The best overall response by the 12-month mark was 78.7% and 76.6%, respectively.

The median follow-up was 21 months. At that point, the median PFS had not been reached in the OB arm but was 14.9 months in the control arm (P<0.0001), according to the independent radiology facility.

According to investigators, the median PFS was 29.2 months and 14 months, respectively (P<0.0001).

The median OS has not been reached in either arm (P=0.4017). Thirty-four patients (18%) in the OB arm died, as did 41 (20%) in the control arm.

Dr Sehn said longer follow-up is needed to determine the potential OS benefit associated with obinutuzumab, but the PFS benefit of OB is clinically meaningful.

“The fact that this new approach doubled average remission time marks a major step forward for our patients,” she said. “Obinutuzumab may offer patients the chance to stay well for a significantly longer period of time, putting off the need for additional chemotherapy.”

 

 

Inside McCormick Place, site of

the 2015 ASCO Annual Meeting

 

CHICAGO—Adding obinutuzumab to treatment with bendamustine improves progression-free survival (PFS) in patients with rituximab-refractory, indolent non-Hodgkin lymphoma (NHL), interim results of the phase 3 GADOLIN trial suggest.

Study investigators said patients who received obinutuzumab and bendamustine followed by obinutuzumab maintenance had roughly double the PFS of patients who received bendamustine alone.

There was no significant difference between the treatment groups with regard to response rates or overall survival (OS), but the investigators said longer follow-up is needed to determine if obinutuzumab confers a benefit in OS.

This trial was stopped before its protocol-specified final analysis because of the PFS benefit observed in the obinutuzumab arm.

Laurie Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, presented these results at the 2015 ASCO Annual Meeting (abstract LBA8502). Genentech Inc. and F. Hoffmann-La Roche Ltd. funded this research.

The trial included 413 patients with rituximab-refractory NHL, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and Waldenstrom’s macroglobulinemia (WM).

The patients were randomized to receive bendamustine alone (120 mg/m²/day on days 1 and 2 for up to six 28-day cycles) or a combination of bendamustine (90 mg/m²/day on days 1 and 2 for up to six 28-day cycles) plus obinutuzumab (1000 mg on days 1, 8, and 15 for cycle 1, followed by 1 dose for up to six 28-day cycles), followed by obinutuzumab maintenance (1000 mg every 2 months for 2 years or until progression).

Dr Sehn said there were no significant differences in baseline characteristics between the treatment arms. Patients in both arms had received a median of 2 prior treatments, and the median time from last treatment was about 4 months.

Of the 194 patients randomized to treatment in the obinutuzumab-bendamustine (OB) arm, 79.9% had FL, 13.9% had MZL, and 6.2% had SLL. Of the 202 patients randomized to the bendamustine-alone (control) arm, 82.2% had FL, 9.4% had MZL, 7.9% had SLL, and 0.5% had WM.

Ultimately, 156 patients completed induction in the OB arm, as did 129 patients in the control arm. Thirty-six patients completed maintenance with obinutuzumab, and 46 were still receiving maintenance at the time of analysis.

Safety results

Dr Sehn said there were no unexpected safety signals among patients in the OB arm.

About 99% of patients in the OB arm experienced at least 1 adverse event (AE), as did 98% of patients in the control arm. Severe AEs occurred in 38.1% and 32.8% of patients, respectively, and grade 3/4 AEs occurred in 67% and 62.1%, respectively.

AEs leading to treatment withdrawal occurred in 18% and 15.7% of patients, respectively. And AEs leading to death occurred in 6.2% and 6.1%, respectively.

Grade 3/4 AEs that occurred in at least 2% of patients in the OB and control arms, respectively, were neutropenia (33% vs 26.3%), thrombocytopenia (10.8% vs 16.2%), infusion-related reactions (10.8% vs 5.6%), anemia (7.7% vs 10.1%), febrile neutropenia (4.6% vs 3.5%), nausea (1% vs 3%), fatigue (1.5% vs 2.5%), diarrhea (1% vs 2.5%), and vomiting (2.1% vs 1%).

Response and survival

According to an independent radiology facility, 69.2% of patients in the OB arm had responded to treatment at the end of induction, as had 63% of the control arm. The best overall response by the 12-month mark was 78.7% and 76.6%, respectively.

The median follow-up was 21 months. At that point, the median PFS had not been reached in the OB arm but was 14.9 months in the control arm (P<0.0001), according to the independent radiology facility.

According to investigators, the median PFS was 29.2 months and 14 months, respectively (P<0.0001).

The median OS has not been reached in either arm (P=0.4017). Thirty-four patients (18%) in the OB arm died, as did 41 (20%) in the control arm.

Dr Sehn said longer follow-up is needed to determine the potential OS benefit associated with obinutuzumab, but the PFS benefit of OB is clinically meaningful.

“The fact that this new approach doubled average remission time marks a major step forward for our patients,” she said. “Obinutuzumab may offer patients the chance to stay well for a significantly longer period of time, putting off the need for additional chemotherapy.”