On April 19, 2023, the U.S. Food and Drug Administration (FDA) approved polatuzumab vedotin-piiq (Polivy®) with rituximab, 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.

FDA Approves Polatuzumab Vedotin-piiq for Previously Untreated Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, and High-Grade B-Cell Lymphoma

Approval was based on POLARIX (NCT03274492), a randomized, double-blind, placebo-controlled trial of 879 patients with previously untreated large B-cell lymphoma and an IPI score of 2–5. The trial evaluated the efficacy of substituting polatuzumab vedotin-piiq for vincristine in the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen. Patients were randomized (1:1) to receive either polatuzumab vedotin-piiq 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). Patients in the pola + R-CHP arm had statistically significant longer PFS (HR = 0.73; 95% CI = 0.57, 0.95; p = 0.0177) and 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 reported by at least 20% of patients treated with pola + R-CHP, excluding laboratory abnormalities, were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. Grade 3–4 laboratory abnormalities reported by at least 10% of patients were lymphopenia, neutropenia, hyperuricemia, and anemia. Peripheral neuropathy developed or worsened in 53% of patients with resolution in 58% after a median of four months. Serious adverse reactions occurred in 34% of patients, including febrile neutropenia and pneumonia.

The recommended dose of polatuzumab vedotin-piiq is 1.8 mg/kg via IV infusion every 21 days for six cycles in combination with R-CHP. Patients should be premedicated with an antihistamine and an antipyretic and receive prophylactic granulocyte–colony-stimulating factor.

View the full prescribing information for polatuzumab vedotin-piiq.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

The application was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.