On 19 April 2023, the US Food and Drug Administration (FDA) approved polatuzumab vedotin-piiq (Polivy, Genentech, Inc.) with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index (IPI) score of 2 or greater.
Full prescribing information for Polivy is available here.
Approval was based on POLARIX (NCT03274492), a randomised, double-blind, placebo-controlled study in 879 patients with previously untreated large B-cell lymphoma and an IPI score of 2-5. The study evaluated the superiority of substituting polatuzumab vedotin for vincristine in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen. Patients were randomised (1:1) to receive either polatuzumab vedotin plus R-CHP (pola + 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 DLBCL, NOS (84%) and HGBL (11%).
Efficacy was based on investigator-assessed progression-free survival (PFS). PFS was statistically significantly longer in the pola + R-CHP arm, with a hazard ratio (HR) of 0.73 (95% confidence interval [CI] 0.57, 0.95; p = 0.0177). This arm also had a statistically significant improvement in modified event-free survival (HR 0.75, 95% CI 0.58, 0.96; p = 0.0244). 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 pola + R-CHP (≥20%), excluding laboratory abnormalities, were peripheral neuropathy, nausea, fatigue, diarrhoea, constipation, alopecia, and mucositis. Grade 3 to 4 laboratory abnormalities (≥10%) were lymphopenia, neutropenia, hyperuricemia, and anaemia. 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 6 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.
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