The Food and Drug Administration (FDA) has approved Polivy® (polatuzumab vedotin-piiq) in combination with rituximab (Rituxan®), cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of 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.
The approval was based on data from the randomized, multicenter, double-blind, placebo-controlled phase 3 POLARIX trial (ClinicalTrials.gov Identifier: NCT03274492), which included adults with previously untreated DLBCL. Patients were randomly assigned to receive either polatuzumab vedotin plus R-CHP for 6 cycles followed by rituximab for 2 cycles (n=440); or the current standard of care rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) for 6 cycles followed by rituximab for 2 cycles (n=439).
After a median follow-up of 24.7 months, treatment with polatuzumab vedotin plus R-CHP was associated with a 27% reduction in the risk of disease progression, relapse or death compared with R-CHOP (hazard ratio [HR], 0.73; 95% CI, 0.57-0.95; P =.0177). Moreover, the progression-free survival (PFS) HR was 0.75 (95% CI, 0.57-0.99) in a prespecified descriptive analysis of the largest lymphoma subgroup, DLBCL, NOS. The PFS HR was 0.48 in patients with HGBL.
A statistically significant improvement in modified event-free survival was also observed in the polatuzumab vedotin plus R-CHP arm compared with R-CHOP (HR 0.75, 95% CI, 0.58-0.96; P =.0244). In the final analysis of overall survival, no statistically significant difference was observed (HR 0.94, 95% CI, 0.67-1.33).
The safety profile of polatuzumab vedotin plus R-CHP was comparable to R-CHOP. The most common adverse events were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. The most common grade 3 to 4 adverse events were lymphopenia, neutropenia, hyperuricemia, and anemia. This decision also converts the accelerated approval of Polivy in combination with bendamustine and Rituxan for relapsed or refractory DLBCL after at least 2 prior therapies to regular approval.
- FDA approves Genentech’s Polivy in combination with R-CHP for people with certain types of previously untreated diffuse large B-cell lymphoma. News release. Genentech. April 19, 2023. Accessed April 20, 2023. https://www.businesswire.com/news/home/20230416005009/en/FDA-Approves-Genentech%E2%80%99s-Polivy-in-Combination-With-R-CHP-for-People-With-Certain-Types-of-Previously-Untreated-Diffuse-Large-B-cell-Lymphoma.
- Package insert. Genentech; 2023. Accessed April 20, 2023. https://www.gene.com/download/pdf/polivy_prescribing.pdf.