On June 10, 2019, the FDA granted accelerated approval to polatuzumab vedotin-piiq (Polivy; Genentech), a CD79b-directed antibody–drug conjugate, in combination with bendamustine (Bendeka, Treanda) plus rituximab (Rituxan or a biosimilar), for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received ≥2 lines of therapy. The FDA granted polatuzumab breakthrough therapy and orphan drug designations.
“Antibody-drug conjugates are an emerging class of targeted immunotherapies for cancer. This type of therapy, unlike traditional chemotherapy, is intended to target specific cells,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Today’s approval of Polivy provides an alternative option for patients in whom multiple treatments have not worked.”
The FDA approval of polatuzumab was based on results from a phase 1b/2 clinical trial of 80 patients with relapsed or refractory DLBCL who received ≥1 previous treatments. Patients were randomized in a 1:1 ratio to polatuzumab plus bendamustine and rituximab or to bendamustine plus rituximab alone for six 21-day cycles.
The efficacy of the polatuzumab based combination regimen was based on complete response rate and duration of response, which was defined as the time the disease remained in remission. The results showed a complete response rate of 40% in the polatuzumab plus bendamustine and rituximab arm versus 18% in the bendamustine plus rituximab alone arm. Of the 25 patients who achieved a partial or a complete response with the polatuzumab-based regimen, 16 (64%) patients had a response lasting ≥6 months and 12 (48%) patients had a response lasting ≥12 months.
The most common (incidence ≥20%) adverse events in patients who received polatuzumab were neutropenia (49%), thrombocytopenia (49%), anemia (47%), peripheral neuropathy (40%), fatigue (40%), diarrhea (38%), pyrexia (33%), decreased appetite (27%), and pneumonia (22%).