Obiutuzumab Receives FDA Approval for Previously Untreated Follicular Lymphoma

On 16 November 2017, the United States Food and Drug Administration FDAapproved obinutuzumab (trade name Gazyva) with chemotherapy for patients with stage II bulky, stage III and stage IV follicular lymphoma who had previously shown at least a partial response (remission) with obinutuzumab monotherapy.

Approval was based on a study involving 1202 patients with previously untreated follicular lymphoma: a multicenter, open-label, randomized phase 3 trial (GALLIUM). Patients were randomized 1:1 to obinutuzumab + chemotherapy or rituximab + chemotherapy, followed by maintenance obinutuzumab or rituximab for 2 years in responding patients.

Among patients with follicular lymphoma, %91 had stage III-IV lymphoma, % 44 had bulky disease and %79 had at least intermediate-risk lymphoma. Of patients, %57 received bendamustine, %33 CHOP and %10 CVP chemotherapy.

With a median follow-up of 38 months, progression-free survival assessed by an independent review committee showed a statistically significant improvement in the obinutuzumab arm compared with the rituximab arm [hazard ratio 0.72 (95% CI: 0.56, 0.93; p=0.0118)].

Median progression-free survival was not reached in either arm. Imaging assessment found similar overall response rates in the obinutuzumab and rituximab arms (%91 with obinutuzumab and %88 with rituximab) and similar complete remission rates (% 28 with obinutuzumab and % 27 with rituximab).

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Safety and side effects were assessed in 1385 patients, with a higher rate of serious adverse events in the obinutuzumab arm than the rituximab arm (%50 versus %43, respectively). The most frequent side effects were infusion reactions, low white blood cell counts, upper respiratory tract infection, cough, constipation and diarrhea. Neutropenia, febrile neutropenia, thrombocytopenia and infusion reactions were the most common serious side effects with obinutuzumab.

In patients with previously untreated follicular lymphoma, the recommended dose of obinutuzumabis, in cycle 1 on days 1, 8 and 15, an intravenous dose of 1000 mg; in cycles 2-6 or 2-8, only on day 1, a dose of 1000 mg; and subsequently every 2 months, 1000 mg for up to 2 years.

How Does Obinutuzumab Work?

Obinutuzumab acts on cancerous B cells, which are part of the immune system, by binding to structures called CD20 on their surfaces. It is a monoclonal antibody medicine. Unlike rituximab, it binds not to conventional type-1 CD20 but to type-2 CD20. This property enables obinutuzumab to induce antibody-dependent cytotoxicity more strongly and provides greater direct cytotoxic effects than conventional CD20 antibodies.

The Figure Below Shows the Mechanisms of Action of Obinutuzumab:

Obinutuzumab (Gazyva) previously received approval on 26 February 2016 for patients with follicular lymphoma that relapsed or was refractory after rituximab treatment. Before that, it had received approval in 2013 for use with chlorambucil in chronic lymphocytic leukemia.