The FDA has approved the CD79b-directed antibody drug conjugate polatuzumab vedotin-piiq, in combination with bendamustine and rituximab (BR), to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received at least two prior therapies.
The approval was based on results from an open-label, multicenter clinical trial that enrolled 80 adult patients and randomized patients 1:1 to receive either BR alone or BR with polatuzumab vedotin-piiq for six 21-day cycles. All participants received rituximab 375 mg/m2 on day one of each cycle, plus bendamustine 90 mg/m2 on days 2-3 of cycle 1 and on days 1-2 of subsequent cycles; in the polatuzumab + BR group, participants also received polatuzumab vedotin-piiq, 1.8 mg/kg by intravenous infusion on day 2 of cycle 1 and on day 1 of subsequent cycles.
The complete response rate, the study’s primary endpoint, was 40% in the polatuzumab + BR group, compared with 18% in the BR-alone group (p value not reported). The overall response rate (including complete and partial responses) was also higher with polatuzumab vedotin-piiq: 63% versus 25%. Among the 25 patients who responded to treatment with polatuzumab vedotin-piiq, 16 (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; occurring in ≥20% of patients) in the polatuzumab group included neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia. Serious AEs occurred in 64% of patients, most often from infection. Cytopenias (seen in 18% of patients) were the most common reason for treatment discontinuation.
Polatuzumab vedotin-piiq was approved with priority review, breakthrough therapy, and orphan drug designations.