Posted: Monday, April 24, 2023
On April 19, the U.S. Food and Drug Administration (FDA) approved polatuzumab vedotin-piiq (Polivy) with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for adults who have previously untreated diffuse large B-cell lymphoma—not otherwise specified or high-grade B-cell lymphoma and who have an International Prognostic Index (IPI) score of at least 2 or greater. This agent is a CD79b-directed antibody-drug conjugate.
Approval was based on the phase III, randomized, double-blind POLARIX trial, which included 879 patients with previously untreated large B-cell lymphoma and an IPI score of between 2 and 5. The trial evaluated the superiority of substituting polatuzumab vedotin for vincristine in the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen.
Efficacy was based on investigator-assessed progression-free survival. In the polatuzumab vedotin–based combination therapy, progression-free survival was statistically significantly longer, with a hazard ratio (HR) of 0.73 (95% confidence interval [CI] = 0.57–0.95; P = .0177). This arm also had a statistically significant improvement in modified event-free survival (HR = 0.75; 95% CI = 0.58–0.96; P = .0244). No significant difference in complete response rate or overall survival (HR = 0.94; 95% CI = 0.67–1.33 on final analysis) was observed.
The most common adverse reactions with the polatuzumab vedotin–based combination therapy (≥ 20%), excluding laboratory abnormalities, were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. Grade 3 to 4 laboratory abnormalities (≥ 10%) were lymphopenia, neutropenia, hyperuricemia, and anemia. Peripheral neuropathy developed or worsened in 53% of patients, with resolution in 58% after a median of 4 months. Serious adverse reactions occurred in 34% of patients, including febrile neutropenia and pneumonia.
The recommended dose of polatuzumab vedotin is 1.8 mg/kg as an intravenous infusion every 21 days for six cycles in combination with R-CHP. Patients should be premedicated with an antihistamine and antipyretic and receive prophylactic granulocyte colony-stimulating factor before treatment with polatuzumab vedotin.
For more information, view the full prescribing information.
U.S. Food and Drug Administration