On April 19, the U.S. Food and Drug Administration (FDA) approved the antibody-drug conjugate polatuzumab vedotin-piiq (Polivy) with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for previously untreated adult patients who have 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 or greater.
Approval was based on POLARIX (ClinicalTrials.gov identifier NCT03274492), a randomized, double-blind, placebo-controlled trial in 879 patients with previously untreated large B-cell lymphoma and an IPI score of 2 to 5. The trial evaluated the superiority of substituting polatuzumab vedotin for vincristine in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen. Patients were randomly assigned 1:1 to receive either polatuzumab vedotin plus R-CHP or R-CHOP for six 21-day cycles, followed by two additional cycles of rituximab alone in both arms. The main diagnoses were de novo diffuse large B-cell lymphoma–not otherwise specified (84%) and high-grade B-cell lymphoma (11%).
Efficacy was based on investigator-assessed progression-free survival. Progression-free survival was statistically significantly longer in the polatuzumab vedotin plus R-CHP arm, 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 seen in patients receiving with polatuzumab vedotin plus R-CHP (occurring in ≥ 20% of patients), excluding laboratory abnormalities, were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. Reported grade 3 to 4 laboratory abnormalities (in ≥ 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.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Orphan Drug designation.