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ASCO 2015: Obinutuzumab Doubles Progression-Free Survival in Patients With Relapsed, Indolent Non-Hodgkin Lymphoma

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Key Points

  • Progression-free survival was 29.2 months for patients with rituximab-refractory indolent non-Hodgkin lymphoma treated with a combination of obinutuzumab and bendamustine vs 14 months with bendamustine alone.
  • The trial was stopped early based on the encouraging results of doubling in progression-free survival.

Adding the anti-CD20 monoclonal antibody obinutuzumab (Gazyva) to standard bendamustine (Treanda) chemotherapy and then following that with single-agent obinutuzumab maintenance therapy “resulted in a statistically significant, but more importantly, a clinically meaningful increase in progression-free survival compared with bendamustine alone,” among patients with rituximab (Rituxan)-refractory indolent non-Hodgkin lymphoma (NHL). The median progression-free survival, as assessed by investigators, was 14 months for bendamustine alone vs 29.2 months for the combination arm.

The primary results from the phase III trial were announced at a press conference at the 2015 ASCO Annual Meeting in Chicago by lead study author Laurie Helen Sehn, MD, MPH, a medical oncologist at the BC Cancer Agency in Vancouver, Canada. She will present a more detailed report at the lymphoma and plasma cell disorders oral session on Monday, June 1 (Abstract LBA8502).

“Unfortunately, there is yet no cure for indolent lymphoma, so the overall goal of treatment is to increase the amount of time patients remain symptom-free and in remission. The fact that this new approach doubled the average remission time marks a major step forward for our patients,” Dr. Sehn stated. “Obinutuzumab may offer patients the chance to stay well for a significantly longer period of time, putting off the need for additional chemotherapy.”

Limited Treatment Options

“It’s encouraging to see such impressive results for a novel anti-CD20 monoclonal antibody in a difficult-to-treat patient population such as those with rituximab-refractory indolent non-Hodgkin lymphoma,” noted ASCO expert Merry-Jennifer Markham, MD. “The fact that this approach stalled cancer progression by more than a year will be good news to patients, who urgently need additional treatment options.” Dr. Markham is an Assistant Professor in the Division of Hematology and Oncology at the University of Florida, Gainesville.

Although the standard initial treatment for indolent NHL is the combination of chemotherapy and the targeted drug rituximab, the majority of patients ultimately become resistant to rituximab, and these patients have limited options for further treatment. Obinutuzumab has been tested in smaller clinical trials in various types of lymphoma, but this is the first randomized phase III trial to assess the potential benefit of obinutuzumab in patients with NHL. The U.S. Food and Drug Administration has recently approved obinutuzumab in combination with chemotherapy for patients with chronic lymphocytic leukemia.

Potential Survival Undetermined

The open-label GADOLIN study included 396 patients and randomly assigned 202 to treatment with bendamustine alone and 194 to a combination of bendamustine and obinutuzumab followed by single-agent obinutuzumab as maintenance therapy. Most patients had follicular lymphoma, but some had marginal zone lymphoma or small lymphocytic lymphoma.

The median age of patients was 63 years, “in keeping with what is typically seen in clinical care of indolent non-Hodgkin lymphoma patients,” Dr. Sehn pointed out. “Importantly, these patients showed a high level of treatment resistance. They had received two median prior lines of therapies, and over 90% of patients in each arm had been designated refractory to their last treatment.”

The primary endpoint of the trial was progression-free survival as determined by an independent review by a radiology facility. Following an interim analysis, the trial was closed “because it had met its primary endpoint,” Dr. Sehn noted. “Patients receiving a combination of obinutuzumab and bendamustine had a significantly improved progression-free survival compared to those receiving bendamustine alone. With a median follow-up of just over 20 months, the median progression-free survival in the bendamustine arm was approximately 14.9 months but had not yet been reached in the combination arm. The hazard ratio was 0.55, indicating a 45% reduction in the rate of progression with the combination therapy.”

Progression-free survival as assessed by investigators was among the secondary endpoints. Median progression-free survival assessed by investigators was 14 months for bendamustine alone vs 29.2 months for the combination arm, “indicating a doubling in progression-free survival,” Dr. Sehn added. 

No Unexpected Safety Concerns

“The safety profile revealed no new safety findings and was in keeping with what we expected with the combination of drugs,” Dr. Sehn noted. For obinutuzumab-bendamustine and bendamustine only, the most common hematologic adverse events were neutropenia (35% vs 29%) and thrombocytopenia (15% vs 24%), and the most common nonhematologic adverse events were infusion-related reactions (69% vs 63%), nausea (54% vs 61%), fatigue (39% vs 33%), and diarrhea (27% vs 30%).  

This study received funding from Genentech Inc. and F. Hoffmann-La Roche Ltd. Dr. Sehn reported honoraria from Roche/Genentech, Celgene, Gilead Sciences, Pfizer, Janssen, Lundbeck, and Amgen; consulting or advisory roles with Roche/Genentech, Celgene, Gilead Sciences, Pfizer, Janssen, Lundbeck, and Amgen; and research funding (institutional) from Roche Pharma AG and Genentech. For full disclosures of the study authors, view the study abstract at abstracts.asco.org.

Watch The ASCO Post Newsreels for an interview with Dr. Sehn recorded live at the 2015 ASCO Annual Meeting.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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