FDA D.I.S.C.O. Burst Edition: FDA approval of Polivy (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) with rituximab, cyclophosphamide, doxorubicin, and prednisone for adults with previously untreated diffuse large B-cell lymphoma (not otherwise specified) or high-grade B-cell lymphoma with an International Prognostic Index score ≥2. Approval was based on the POLARIX trial (n=879), in which substituting polatuzumab for vincristine improved investigator-assessed progression-free survival (HR 0.73); overall survival was not significantly different.

FDA approval (Apr 19, 2023)

The FDA approved polatuzumab vedotin-piiq (Polivy) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone for adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified, or high-grade B-cell lymphoma who have an International Prognostic Index (IPI) score ≥2.

Key evidence: POLARIX

Approval was based on POLARIX, a randomized, double-blind, placebo-controlled trial enrolling 879 patients with previously untreated large B-cell lymphoma and IPI 2–5. Patients were randomized 1:1 to receive:

  • Polatuzumab vedotin + R-CHP (polatuzumab substituted for vincristine) for six 21-day cycles, or
  • R-CHOP for six 21-day cycles, followed by two additional cycles of rituximab alone in both arms.

Efficacy was based on investigator-assessed progression-free survival (PFS), which was statistically significantly longer with polatuzumab (HR 0.73). Modified event-free survival was also statistically significantly improved. No significant differences were observed in complete response rate or overall survival.

Safety highlights

Common adverse reactions (>20%; excluding lab abnormalities) included peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. Grade 3–4 lab abnormalities (>10%) included lymphopenia, neutropenia, hyperuricemia, and anemia. Peripheral neuropathy developed or worsened in 53% (resolved in 58% after a median of 4 months). Serious adverse reactions occurred in 34%, including febrile neutropenia and pneumonia.

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