On April 19, 2023, the FDA approved polatuzumab vedotin (Polivy; Genentech), a CD79b-directed antibody–drug conjugate, in combination with rituximab (Rituxan or a biosimilar; Genentech), cyclophosphamide, doxorubicin, and prednisone (R-CHP) for adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified, or high-grade B-cell lymphoma and who have an International Prognostic Index (IPI) score of ≥2.
The FDA granted polatuzumab vedotin accelerated approval in June 2019 for use in combination with bendamustine (Bendeka, Treanda) plus rituximab for the treatment of patients with relapsed or refractory DLBCL after ≥2 previous therapies. The FDA decision in April 2023 converts that accelerated approval to a regular approval.
“It has been nearly 20 years since a new treatment option has become available to people newly diagnosed with diffuse large B-cell lymphoma,” Levi Garraway, MD, PhD, Chief Medical Officer and Head of Global Product Development, Roche, stated in a news release. “Today’s decision from the FDA to approve Polivy in combination with R-CHP in this setting brings a much-needed new treatment option which may improve outcomes and bring other benefits to many patients with this aggressive lymphoma.”
The new approval was based on data from the POLARIX study, a randomized, double-blind, placebo-controlled clinical trial of 879 patients with previously untreated large B-cell lymphoma and an IPI score of 2 to 5. Patients were randomized (1:1) to receive polatuzumab vedotin plus R-CHP or rituximab, cyclophosphamide, doxorubicin, vincristine, plus prednisone (R-CHOP) for six 21-day cycles, followed by 2 additional cycles of rituximab alone in both arms.
The primary end point was investigator-assessed progression-free survival (PFS). Key secondary end points included event-free survival, end-of-treatment positron emission tomography–computed tomography, complete response rate, disease-free survival, overall survival, and safety.
Treatment with polatuzumab vedotin plus R-CHP significantly lowered the risk for disease progression or death compared with R-CHOP (stratified hazard ratio, 0.73; 95% confidence interval, 0.57-0.95; P =.02). At a median follow-up of 28.2 months, the PFS rate was 24.3% in the polatuzumab vedotin plus R-CHP arm versus 30.5% in the R-CHOP arm.
The most common any-grade adverse reactions in the polatuzumab vedotin plus R-CHP and R-CHOP arms were peripheral neuropathy (52.9% vs 53.9%, respectively), nausea (41.6% vs 36.8%, respectively), neutropenia (30.8% vs 32.6%, respectively), and diarrhea (30.8% vs 20.1%, respectively).