FDA Grants Approval to Polatuzumab Vedotin for Patients With Previously Untreated DLBCL and High-Grade B-Cell Lymphoma

On April 19, 2023, polatuzumab vedotin-piiq in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) was approved by the Food and Drug Administration (FDA) as treatment for adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), or high-grade B-cell lymphoma (HGBL) and an International Prognostic Index (IPI) score of 2 to 5. 

The FDA granted this approval based on the results of the randomized, double-blind, placebo-controlled POLARIX trial (NCT03274492), which aimed to evaluate the superiority of treatment with polatuzumab vedotin over vincristine in the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen. 

The trial evaluated the superiority of substituting polatuzumab vedotin for vincristine in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen. In the trial, 879 patients were randomized 1 to 1 to receive either polatuzumab vedotin plus R-CHP (rituximab, cyclophosphamide, doxorubicin, and prednisone) or R-CHOP over the course of 6 21-day cycles, followed by 2 additional cycles of rituximab alone in both arms. The main diagnoses were de novo DLBCL, NOS (84%) and HGBL (11%).

The efficacy was based on investigator-assessed progression-free survival (PFS). PFS was statistically significantly longer in the polatuzumab vedotin + R-CHP arm, with a hazard ratio of 0.73 (95% confidence interval [CI], 0.57 to 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 to 0.96; p=0.0244). No significant difference in complete response rate or overall survival (HR 0.94; 95% CI, 0.67 to 1.33 on final analysis) was observed.

In terms of safety in the polatuzumab vedotin plus R-CHP arm, the most common adverse reactions (excluding laboratory abnormalities) observed were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. Grade 3 to 4 laboratory abnormalities in this arm included lymphopenia, neutropenia, hyperuricemia, and anemia. 34% of patients experienced serious adverse reactions, including febrile neutropenia and pneumonia.

Source: 

FDA approves polatuzumab vedotin-piiq for previously untreated diffuse large B-cell lymphoma, not otherwise specified, and high-grade B-cell lymphoma. Press Release. The US Food and Drug Administration. Published online April 20, 2023. Accessed April 20, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-previously-untreated-diffuse-large-b-cell-lymphoma-not