Tuesday, August 25, 2015

Obinutuzumab in Follicular Lymphoma

The Journal of Clinical Oncology has an early release version for an article called "Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study."As the title suggests, this is a report from the phase II clinical trial that compared Rituxan and Obinutuzumab.

A little background first. Obinutuzumab, like Rituxan, is a monoclonal antibody that targets CD20, a protein on the surface of Follicular Lymphoma cells (and other lymphoma cells). There have been several attempts to find a monoclonal antibody that can do a better job than Rituxan, but so far, there's no clear winner (and this study seems to show that Obinutuzumab isn't a big improvement on Rituxan either).

Obinutuzumab (also known as GA101 in the past, and Gazyva in the future) is different from Rituxan in a couple of ways. First, it is humanized, formed from human cells (Rituxan comes from mouse cells), so the thought was that it would cause fewer allergic reactions. Second, it is glycoengineered, which means they have had sugar molecules attached to them in a way that makes them more effective. (You can find out more about that process from this fun little video involving an antibody beauty contest, a mouse with an umbrella, and a five year old girl dressed like a ballerina with dinosaurs on her dress.) Obinutuzumab has been designated as a Breakthrough Therapy by the FDA for CLL. But, again, it seems less effective on Follicular Lymphoma.

The phase II study involved 175 patients with relapsed CD20-positive indolent lymphoma; the great majority of them (149) had Follicular Lymphoma. All patients had already had a response to a treatment that contained Rituxan. Half the patients in the study received Obinutuzumaband half received Rituxan, both of them once a week for four weeks.

For the FL patients, the good news was that more of them had a response to Obinutuzumab -- 44%, while only 33% of the Rituxan patients had a response. When an independent panel looked at the results, the difference was even bigger: 44% responded to Obinutuzuma, but only 26% to Rituxan. So by that measure, Obinutuzumab does seem more effective.

The bad news, though, was in how effective it was for individual patients who did have a response -- there was no real difference between the two groups in their Progression Free Survival. In other words, patients in both groups went the same amount of time before the disease came back. Not much difference in safety between the two groups, except that the Obinutuzumab group had more infusion-related reactions and cough.

The authors of the article believe the higher Overall Response Rate is enough to justify a phase III clinical trial.

What this means, of course, is that Obinutuzumab may not be the best choice for this population -- Follicular Lymphoma patients who had already had treatment that contained Rituxan. There are other trials out there, including one that was reported at ASCO this year, from the Gadolin trial, which found significant improvement in PFS when Obinutuzumab was added to Bendamustine (versus Bendamustine on its own).

So we won't give up on Obinutuzumab just yet. It's a good reminder that all of this is going to take time, and our job is to stay informed and support Follicular Lymphoma research in any way we can.

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