Obinutuzumab Equals Rituximab in Relapsed Indolent NHL

SAN DIEGO – Induction therapy with obinutuzumab, a bioengineered CD20 inhibitor, induced a slightly higher overall response rate in induction therapy than did rituximab in patients with relapsed, CD20-positive indolent B-cell non-Hodgkin’s lymphoma, investigators reported at the annual meeting of the American Society of Hematology.

According to independent radiology reviewers who were blinded to treatment type, the overall response rate – a composite of complete responses (CR), CR-unconfirmed (CRu), and partial responses – was 44.6% at the end of induction among 74 patients with follicular lymphoma that was treated with obinutuzumab (Genentech’s GA101), compared with 26.7% of patients on rituximab (Rituxan) (P = .01), said Dr. Laurie H. Sehn, a medical oncologist at the University of British Columbia, Vancouver.

However, the overall response rate (ORR) by trial investigator ratings – the primary end point – showed a trend that was not significant, at 44.6% vs. 33.3% (P = .08). There is currently no difference in progression-free survival, said Dr. Sehn, on behalf of her colleagues in the phase II GAUSS trial, touted at the first head-to-head comparison of the two anti-CD20 antibodies.

Patients with other indolent lymphoma histologies were included in the trial, but Dr. Sehn reported full data on patients with follicular lymphomas only.

Obinutuzumab is considered to be a type II monoclonal antibody, shown in preclinical testing to have better ability than does rituximab to cause cell death and to invoke a cellular immune response, with lower complement-dependent cytotoxicity, Dr, Sehn said at a briefing on Dec. 11 in advance of presentation of the results on Dec. 12, 2011.

"As a single drug, rituximab really has had one of the most significant impacts in outcome in B-cell lymphomas in probably the last several decades, so there’s a real motivation to take it one step further and possibly develop a new anti-CD20 antibody that might work better than rituximab or one that may continue to work when rituximab stops working, so as to further improve outcomes," Dr, Sehn said.

A lymphoma specialist who was not involved in the GAUSS trial commented that despite rituximab’s significant benefits, new treatments still are needed, but whether obinutuzumab or another pretender is heir to rituximab’s throne is still unclear.

"We’ve been waiting for a better rituximab for some period of time. It has certainly been the major advance in the therapy of lymphomas in the last 10 to 12 years. The question is, can we do better? Genentech has made an attempt with obinutuzumab to improve the outcome for these patients who are still rituximab-sensitive," commented Dr. Ephraim P. Hochberg of the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.

"The results are not overwhelming: there’s certainly a trend toward better progression-free survival, there’s a trend toward a slightly improved response rate, and a trend toward a slightly improved complete response rate, but this doesn’t look to be the home run that we might have hoped for with this patient population," he said.

The GAUSS trial is an ongoing, open-label, phase II study. Patients with relapsed CD20+ NHL who had a prior response lasting at least 6 months to a rituximab-containing regimen were randomly assigned to receive either rituximab 375 mg/m² IV weekly for 4 weeks or obinutuzumab 1 g IV weekly for 4 weeks. At the end of the induction phase, patients were assessed and those without disease progression continued with maintenance therapy on the same drug and dose every 2 months for up to 2 years.

In addition to the primary end point results shown above, they found that the best overall response rates by investigator determination occurred in 66.2% of patients on obinutuzumab (35.1% CR/Cru, and 31.1% partial response), and 64% among those on rituximab (18.7% CR/Cru, and 45.3% PR; P = .39). By independent review, the best ORR was 60.8% with obinutuzumab (27% CR/Cru, 33.8% PR), and 46.7% with rituximab (20% and 26.7%; P = .04).*

There were no differences in progression-survival with 39.2% of patients on obinutuzumab having an event at a median time to event of 17.3 months, compared with 34.7% of patients on rituximab with a median time to event of 17.4 months.

In the obinutuzumab arm, 93% of patients had at least one adverse event vs. 81% in the rituximab arm. There were no adverse events leading to death within 28 months of the last dose of obinutuzumab compared with 2 patients on rituximab. Adverse events leading to withdrawal occurred in 8% and 10%, respectively. The proportion of patients having at least one adverse event in each group was identical, at 14%.

Phase III trials with obinutuzumab are underway.

The study was supported by Roche. Dr. Sehn and three coauthors disclosed consulting and receiving honoraria and/or research funding from Roche/Genentech. Two coauthors are Roche employees. Dr. Hochberg has received consulting fees or research support from the company.

*Correction, 12/15/2011: The best overall response rate by independent review was incorrectly stated for rituximab. This version has been updated.

SAN DIEGO – Induction therapy with obinutuzumab, a bioengineered CD20 inhibitor, induced a slightly higher overall response rate in induction therapy than did rituximab in patients with relapsed, CD20-positive indolent B-cell non-Hodgkin’s lymphoma, investigators reported at the annual meeting of the American Society of Hematology.

According to independent radiology reviewers who were blinded to treatment type, the overall response rate – a composite of complete responses (CR), CR-unconfirmed (CRu), and partial responses – was 44.6% at the end of induction among 74 patients with follicular lymphoma that was treated with obinutuzumab (Genentech’s GA101), compared with 26.7% of patients on rituximab (Rituxan) (P = .01), said Dr. Laurie H. Sehn, a medical oncologist at the University of British Columbia, Vancouver.

However, the overall response rate (ORR) by trial investigator ratings – the primary end point – showed a trend that was not significant, at 44.6% vs. 33.3% (P = .08). There is currently no difference in progression-free survival, said Dr. Sehn, on behalf of her colleagues in the phase II GAUSS trial, touted at the first head-to-head comparison of the two anti-CD20 antibodies.

Patients with other indolent lymphoma histologies were included in the trial, but Dr. Sehn reported full data on patients with follicular lymphomas only.

Obinutuzumab is considered to be a type II monoclonal antibody, shown in preclinical testing to have better ability than does rituximab to cause cell death and to invoke a cellular immune response, with lower complement-dependent cytotoxicity, Dr, Sehn said at a briefing on Dec. 11 in advance of presentation of the results on Dec. 12, 2011.

"As a single drug, rituximab really has had one of the most significant impacts in outcome in B-cell lymphomas in probably the last several decades, so there’s a real motivation to take it one step further and possibly develop a new anti-CD20 antibody that might work better than rituximab or one that may continue to work when rituximab stops working, so as to further improve outcomes," Dr, Sehn said.

A lymphoma specialist who was not involved in the GAUSS trial commented that despite rituximab’s significant benefits, new treatments still are needed, but whether obinutuzumab or another pretender is heir to rituximab’s throne is still unclear.

"We’ve been waiting for a better rituximab for some period of time. It has certainly been the major advance in the therapy of lymphomas in the last 10 to 12 years. The question is, can we do better? Genentech has made an attempt with obinutuzumab to improve the outcome for these patients who are still rituximab-sensitive," commented Dr. Ephraim P. Hochberg of the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.

"The results are not overwhelming: there’s certainly a trend toward better progression-free survival, there’s a trend toward a slightly improved response rate, and a trend toward a slightly improved complete response rate, but this doesn’t look to be the home run that we might have hoped for with this patient population," he said.

The GAUSS trial is an ongoing, open-label, phase II study. Patients with relapsed CD20+ NHL who had a prior response lasting at least 6 months to a rituximab-containing regimen were randomly assigned to receive either rituximab 375 mg/m² IV weekly for 4 weeks or obinutuzumab 1 g IV weekly for 4 weeks. At the end of the induction phase, patients were assessed and those without disease progression continued with maintenance therapy on the same drug and dose every 2 months for up to 2 years.

In addition to the primary end point results shown above, they found that the best overall response rates by investigator determination occurred in 66.2% of patients on obinutuzumab (35.1% CR/Cru, and 31.1% partial response), and 64% among those on rituximab (18.7% CR/Cru, and 45.3% PR; P = .39). By independent review, the best ORR was 60.8% with obinutuzumab (27% CR/Cru, 33.8% PR), and 46.7% with rituximab (20% and 26.7%; P = .04).*

There were no differences in progression-survival with 39.2% of patients on obinutuzumab having an event at a median time to event of 17.3 months, compared with 34.7% of patients on rituximab with a median time to event of 17.4 months.

In the obinutuzumab arm, 93% of patients had at least one adverse event vs. 81% in the rituximab arm. There were no adverse events leading to death within 28 months of the last dose of obinutuzumab compared with 2 patients on rituximab. Adverse events leading to withdrawal occurred in 8% and 10%, respectively. The proportion of patients having at least one adverse event in each group was identical, at 14%.

Phase III trials with obinutuzumab are underway.

The study was supported by Roche. Dr. Sehn and three coauthors disclosed consulting and receiving honoraria and/or research funding from Roche/Genentech. Two coauthors are Roche employees. Dr. Hochberg has received consulting fees or research support from the company.

*Correction, 12/15/2011: The best overall response rate by independent review was incorrectly stated for rituximab. This version has been updated.

SAN DIEGO – Induction therapy with obinutuzumab, a bioengineered CD20 inhibitor, induced a slightly higher overall response rate in induction therapy than did rituximab in patients with relapsed, CD20-positive indolent B-cell non-Hodgkin’s lymphoma, investigators reported at the annual meeting of the American Society of Hematology.

According to independent radiology reviewers who were blinded to treatment type, the overall response rate – a composite of complete responses (CR), CR-unconfirmed (CRu), and partial responses – was 44.6% at the end of induction among 74 patients with follicular lymphoma that was treated with obinutuzumab (Genentech’s GA101), compared with 26.7% of patients on rituximab (Rituxan) (P = .01), said Dr. Laurie H. Sehn, a medical oncologist at the University of British Columbia, Vancouver.

However, the overall response rate (ORR) by trial investigator ratings – the primary end point – showed a trend that was not significant, at 44.6% vs. 33.3% (P = .08). There is currently no difference in progression-free survival, said Dr. Sehn, on behalf of her colleagues in the phase II GAUSS trial, touted at the first head-to-head comparison of the two anti-CD20 antibodies.

Patients with other indolent lymphoma histologies were included in the trial, but Dr. Sehn reported full data on patients with follicular lymphomas only.

Obinutuzumab is considered to be a type II monoclonal antibody, shown in preclinical testing to have better ability than does rituximab to cause cell death and to invoke a cellular immune response, with lower complement-dependent cytotoxicity, Dr, Sehn said at a briefing on Dec. 11 in advance of presentation of the results on Dec. 12, 2011.

"As a single drug, rituximab really has had one of the most significant impacts in outcome in B-cell lymphomas in probably the last several decades, so there’s a real motivation to take it one step further and possibly develop a new anti-CD20 antibody that might work better than rituximab or one that may continue to work when rituximab stops working, so as to further improve outcomes," Dr, Sehn said.

A lymphoma specialist who was not involved in the GAUSS trial commented that despite rituximab’s significant benefits, new treatments still are needed, but whether obinutuzumab or another pretender is heir to rituximab’s throne is still unclear.

"We’ve been waiting for a better rituximab for some period of time. It has certainly been the major advance in the therapy of lymphomas in the last 10 to 12 years. The question is, can we do better? Genentech has made an attempt with obinutuzumab to improve the outcome for these patients who are still rituximab-sensitive," commented Dr. Ephraim P. Hochberg of the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.

"The results are not overwhelming: there’s certainly a trend toward better progression-free survival, there’s a trend toward a slightly improved response rate, and a trend toward a slightly improved complete response rate, but this doesn’t look to be the home run that we might have hoped for with this patient population," he said.

The GAUSS trial is an ongoing, open-label, phase II study. Patients with relapsed CD20+ NHL who had a prior response lasting at least 6 months to a rituximab-containing regimen were randomly assigned to receive either rituximab 375 mg/m² IV weekly for 4 weeks or obinutuzumab 1 g IV weekly for 4 weeks. At the end of the induction phase, patients were assessed and those without disease progression continued with maintenance therapy on the same drug and dose every 2 months for up to 2 years.

In addition to the primary end point results shown above, they found that the best overall response rates by investigator determination occurred in 66.2% of patients on obinutuzumab (35.1% CR/Cru, and 31.1% partial response), and 64% among those on rituximab (18.7% CR/Cru, and 45.3% PR; P = .39). By independent review, the best ORR was 60.8% with obinutuzumab (27% CR/Cru, 33.8% PR), and 46.7% with rituximab (20% and 26.7%; P = .04).*

There were no differences in progression-survival with 39.2% of patients on obinutuzumab having an event at a median time to event of 17.3 months, compared with 34.7% of patients on rituximab with a median time to event of 17.4 months.

In the obinutuzumab arm, 93% of patients had at least one adverse event vs. 81% in the rituximab arm. There were no adverse events leading to death within 28 months of the last dose of obinutuzumab compared with 2 patients on rituximab. Adverse events leading to withdrawal occurred in 8% and 10%, respectively. The proportion of patients having at least one adverse event in each group was identical, at 14%.

Phase III trials with obinutuzumab are underway.

The study was supported by Roche. Dr. Sehn and three coauthors disclosed consulting and receiving honoraria and/or research funding from Roche/Genentech. Two coauthors are Roche employees. Dr. Hochberg has received consulting fees or research support from the company.

*Correction, 12/15/2011: The best overall response rate by independent review was incorrectly stated for rituximab. This version has been updated.