FDA approves polatuzumab vedotin-piiq for previously untreated diffuse large B-cell lymphoma, not otherwise specified, and high-grade B-cell lymphoma
Regulatory approval: On April 19, 2023, the FDA approved polatuzumab vedotin-piiq (Polivy) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified, or high-grade B-cell lymphoma (HGBL) with International Prognostic Index (IPI) score ≥2. Approval was based on the phase 3 POLARIX trial showing improved investigator-assessed progression-free survival versus R-CHOP.
FDA approval (2023-04-19): Polatuzumab vedotin-piiq + R-CHP in untreated DLBCL NOS/HGBL
On April 19, 2023, the FDA approved polatuzumab vedotin-piiq (Polivy; Genentech) with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for adult patients with previously untreated DLBCL, not otherwise specified (NOS), or high-grade B-cell lymphoma (HGBL) who have an IPI score ≥2.
Supporting evidence
Approval was based on POLARIX (NCT03274492), a randomized, double-blind, placebo-controlled trial in 879 patients with previously untreated large B-cell lymphoma and IPI 2–5. Polatuzumab vedotin replaced vincristine in R-CHOP (i.e., pola + R-CHP vs R-CHOP) for six 21-day cycles, followed by two cycles of rituximab alone in both arms. Key diagnoses were de novo DLBCL NOS (84%) and HGBL (11%).
- Progression-free survival (primary, investigator-assessed): HR 0.73 (95% CI, 0.57–0.95; p=0.0177)
- Modified event-free survival: HR 0.75 (95% CI, 0.58–0.96; p=0.0244)
- Overall survival: HR 0.94 (95% CI, 0.67–1.33; final analysis), no significant difference
Safety and dosing (from FDA labeling)
Common adverse reactions (≥20%; excluding labs) included peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. Serious adverse reactions occurred in 34% (including febrile neutropenia and pneumonia). Recommended dosing: 1.8 mg/kg IV every 21 days for 6 cycles with R-CHP; labeling notes premedication (antihistamine/antipyretic) and G-CSF prophylaxis.