Conference Coverage

Obinutuzumab vs. rituximab weighed as follicular lymphoma therapy



– Does obinutuzumab have a leg up over rituximab for treating follicular lymphoma?

A strict reading of the efficacy records of the two anti-CD20 antibodies when they went head-to-head suggests that obinutuzumab (Gazyva) edged out rituximab (Rituxan), but a broader view leaves the door open for rituximab as a still viable option depending on a patient’s status and priorities, experts said at the conference held by Imedex.

Dr. John P. Leonard

Dr. John P. Leonard

For the roughly 80% of patients with follicular lymphoma (indolent non-Hodgkin lymphoma) who die with their disease rather than from it, management needs to focus on quality of life issues as much as on efficacy, said John P. Leonard, MD, professor of medicine at Weill Cornell Medicine, New York.

While conceding that quality of life correlates with progression-free survival (PFS), he stressed that it also correlates with treatment toxicities, treatment duration, and disease-related side effects.

Trial results have indicated that patients with newly diagnosed follicular lymphoma are reasonably treated with rituximab alone, or with rituximab plus bendamustine, without need for maintenance therapy, Dr. Leonard said.

In contrast, GALLIUM, a phase III trial that compared rituximab against obinutuzumab, used a maintenance phase of monotherapy with each of these two drugs following an induction phase when each of the drugs was combined with chemotherapy.

“If you use this approach [tested in GALLIUM] you need to use maintenance therapy,” and it was in GALLIUM that the most dramatic efficacy advantage for obinutuzumab over rituximab appeared, in the form of longer PFS although, so far, without demonstrated advantage in overall survival. The GALLIUM results, reported in December 2016 at the American Society of Hematology meeting, showed a 3-year PFS rate of 80% among patients treated with obinutuzumab and 73% among those treated with rituximab, a hazard ratio of 0.66 in favor of obinutuzumab that was statistically significant (P = .001) for the study’s primary endpoint (Blood. 2016 Dec 4;abstract 6).

“If you follow this study, you commit the patient to maintenance. We need to talk with patients about the pros and cons of maintenance, the pros and cons of chemotherapy, and the pros and cons of single agent therapy” with one of these anti-CD20 antibodies, Dr. Leonard said. “Right now, I think it’s unclear which antibody is best,” he concluded

Dr. Jonathan W. Friedberg

Dr. Jonathan W. Friedberg

On the other hand, for Jonathan W. Friedberg, MD, the PFS advantage from obinutuzumab in GALLIUM trumps other concerns. “Based upon the GALLIUM data for symptomatic, aggressive follicular lymphoma obinutuzumab plus chemotherapy is the best option to achieve prolonged PFS,” said Dr. Friedberg, professor of medicine and director of the Wilmot Cancer Institute at the University of Rochester (N.Y.).

To further buttress the case for obinutuzumab, he also cited the higher response rate among relapsed patients when single-agent obinutuzumab went against single-agent rituximab (J Clin Oncol. 2015 Oct 20:33[30]:3467-74), and the overall survival advantage that obinutuzumab gave patients when combined with bendamustine in patients refractory to rituximab (Blood. 2016 Dec 5; abstract 615).

Agreeing that the design of GALLIUM focused on combining an anti-CD20 antibody with chemotherapy, Dr. Friedberg acknowledged that, as initial therapy, “using rituximab monotherapy is very reasonable for many patients. I divide [follicular lymphoma] patients into those who are very symptomatic” (for example, those with hydronephrosis) “and need chemotherapy, and those who are not that symptomatic for whom single-agent rituximab is very reasonable,” he said in an interview.

Tumor aggressiveness is another way to identify patients who need chemotherapy plus an antibody, he added. “If the patient is not symptomatic, I generally first observe them, and if the growth is slow, you can sometimes intervene with rituximab alone, but, if the growth is fast, you also need chemotherapy,” Dr. Friedberg said.

Cost may soon become another consideration now that the U.S. patent on rituximab has expired leading to the ongoing development of several biosimilar versions of the antibody. If biosimilar formulations of rituximab soon appear on the U.S. market and if they result in a significant drop in drug price, it would introduce yet another significant variable. “Presuming biosimilar rituximab lowers the cost, that would be another important treatment decision,” he said.

Dr. Friedberg has been a consultant to Bayer. Dr. Leonard has been a consultant to 13 drug companies. Neither disclosed a relationship with the companies that market obinutuzumab or rituximab.

On Twitter @mitchelzoler

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