Obinutuzumab Approved by the FDA for Follicular Lymphoma

Jason M. Broderick

Obinutuzumab (Gazyva) plus bendamustine, followed by obinutuzumab alone has been approved by the FDA as a treatment of patients with follicular lymphoma who were not responsive to a rituximab regimen, or who relapsed after rituximab-based therapy.

Sandra Horning, MD

Obinutuzumab (Gazyva) plus bendamustine, followed by obinutuzumab alone as a treatment of patients with follicular lymphoma who were not responsive to a rituximab regimen, or who relapsed after rituximab-based therapy, has been approved by the FDA. according to Genentech, the manufacturer of the anti-CD20 agent.

According to he manufacturer of the anti-CD20 agent, Genentech, the approval of obinutuzumab is based on the phase III GADOLIN study, where obinutuzumab plus bendamustine followed by obinutuzumab reduced the risk of disease progression by 52% compared with bendamustine alone (HR = 0.48; 95% CI 0.34-0.68; P <.0001) in patients with follicular lymphoma who progressed on a rituximab-based treatment.

"People with follicular lymphoma whose disease returns or worsens despite treatment with a Rituxan-containing regimen need more options because the disease becomes more difficult to treat each time it comes back," said Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech. "Gazyva plus bendamustine provides a new treatment option that can be used after relapse to significantly reduce the risk of progression or death."

The multicenter, open-label, phase III GADOLIN study involved 413 patients with rituximab-refractory iNHL, the most common being follicular lymphoma (n = 321). Patients were considered rituximab-refractory if they did not respond to either rituximab monotherapy or rituximab in combination with chemotherapy, or had relapsed within 6 months of completion of the last dose of a rituximab-based regimen (rituximab monotherapy or rituximab plus chemotherapy).

Patients in the experimental arm received bendamustine (90 mg/m2 IV on days 2 and 3 of cycle 1, and days 1 and 2 of cycles 2-6) plus 6 cycles of obinutuzumab (1000 mg IV on days 1, 8, and 15 of cycle 1, and day 1 of cycles 2-6) followed by obinutuzumab every 2 months until disease progression for a maximum of 2 years. In the comparator group, patients received 6 cycles of bendamustine monotherapy (120 mg/m2 IV on days 1 and 2 of cycles 1-6). The cycle length for both treatment arms was 28 days.

Clinical characteristics across both arms of the study were comparable: median patient age was 63 years, with a median two prior lines of therapy; approximately 4 months had elapsed since their last treatment. More than 90% of patients in each arm were refractory to their last treatment.

The primary endpoint of the study was progression-free survival (PFS). Secondary outcome measures included overall survival, response, and safety.

The median PFS, as determined by an independent panel, was not reached in the obinutuzumab arm versus 13.8 months in the control arm. By investigator assessment, the median PFS with obinutuzumab was 29.2 months versus 13.7 months (HR = 0.48; 95% CI, 0.35-0.67,P<.0001).