FDA Approves Polivy™, First Chemoimmunotherapy for DLBCL

The U.S. Food and Drug Administration granted accelerated approval to Polivy™ (polatuzumab vedotin-piiq), a CD79b-directed antibody-drug conjugate, in combination with bendamustine and rituximab for adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, who received at least two prior therapies.

The decision was based on the multicenter, phase Ib/II GO29365 trial that included 80 patients with relapsed/refractory DLBCL who received at least one prior regimen. Patients were randomized 1:1 to receive polatuzumab vedotin-piiq in combination with bendamustine and rituximab (n=40) or bendamustine plus rituximab alone (n=40) for six 21-day cycles.

Polatuzumab vedotin-piiq 1.8 mg/kg was administered via intravenous infusion on day two of cycle one and on day one of subsequent cycles. Bendamustine 90 mg/m2 was administered intravenously on days two and three of cycle one and on days one and two of subsequent cycles. Rituximab 375 mg/m2 was administered intravenously on day one of each cycle.

After therapy, the complete response (CR) rate was 40% (95% CI, 25-57) in the cohort receiving the polatuzumab vedotin-piiq combination versus 18% (95% CI, 7-33%) in those receiving bendamustine plus rituximab alone. The best overall response rate was 63% and 25%, respectively. Of the 25 patients who achieved partial response or CR following the polatuzumab vedotin-piiq combination therapy, 16 patients (64%) had response durations of at least six months and 12 (48%) had response durations of at least 12 months.

The most common adverse events (AEs) associated with polatuzumab vedotin-piiq were neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia. Serious AEs occurred in 64% of these patients, most often from infection. Cytopenia was the most common reason for treatment discontinuation (18%).

The prescribing information for polatuzumab vedotin-piiq carries warnings and precautions for peripheral neuropathy, infusion-related reactions, myelosuppression, serious and opportunistic infections, progressive multifocal leukoencephalopathy, tumor lysis syndrome, hepatotoxicity, and embryo-fetal toxicity.