On April 19, 2023, the FDA approved a new indication for polatuzumab vedotin-piiq (Polivy; Genentech) with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for adults with previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified, or high-grade B-cell lymphoma and an International Prognostic Index (IPI) score of ≥2. Polatuzumab vedotin, a CD79b-directed antibody–drug conjugate, is the newest FDA-approved option for the first-line treatment of DLBCL in almost 20 years.
The FDA granted this indication an orphan drug designation.
This approval also grants regular approval status to polatuzumab vedotin’s previous accelerated approval, in combination with bendamustine and rituximab, for relapsed or refractory DLBCL, not otherwise specified, after ≥2 lines of therapy.
The current approval was based on the results of the phase 3 POLARIX (NCT03274492) study, a randomized, double-blind, placebo-controlled trial that evaluated the superiority of substituting polatuzumab vedotin for vincristine in the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in patients with previously untreated large B-cell lymphoma and an IPI score of 2 to 5. A total of 879 patients were randomized (1:1) to polatuzumab vedotin plus R-CHP or to R-CHOP for six 21-day cycles, followed by 2 additional cycles of rituximab alone in both groups. Most patients had de novo DLBCL, not otherwise specified (84%), or high-grade B-cell lymphoma (11%).
Efficacy was based on investigator-assessed progression-free survival, which was significantly longer in patients receiving polatuzumab vedotin plus R-CHP than in patients who received polatuzumab vedotin plus R-CHOP, with a hazard ratio (HR) of 0.73 (95% confidence interval [CI], 0.57-0.95; P=.0177). There was also a significant improvement in modified event-free survival (HR, 0.75; 95% CI, 0.58-0.96; P=.0244) in the group that received polatuzumab vedotin plus R-CHP versus the group that received vedotin plus R-CHOP. No significant differences were noted in complete response rate or overall survival between the groups (HR, 0.94; 95% CI, 0.67-1.33 on final analysis).
With polatuzumab vedotin plus R-CHP, the most common (≥20%) adverse reactions, excluding laboratory abnormalities, were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. The grade 3 or 4 laboratory abnormalities (≥10%) included lymphopenia, neutropenia, hyperuricemia, and anemia. A total of 53% of patients had new or worsened peripheral neuropathy, and 58% had resolution of peripheral neuropathy after a median of 4 months. Overall, 34% of patients had serious adverse events, including febrile neutropenia and pneumonia.
The recommended dose of polatuzumab vedotin is 1.8 mg/kg infused intravenously every 21 days for 6 cycles with R-CHP. Patients should receive premedication with an antihistamine and antipyretic drug, as well as a prophylactic granulocyte colony-stimulating factor, before treatment with polatuzumab vedotin.