FDA Accepts sBLA for Polatuzumab Vedotin Combination in Previously Untreated DLBCL

By April 2023, the FDA plans have a decision on the approval application for polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone as an option for treatment-naïve diffuse large B-cell lymphoma.

The FDA has accepted a supplemental biologics license application (sBLA) for polatuzumab vedotin-piiq (Polivy) in combination with rituximab (Rituxan), cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL).1

The sBLA is supported by findings from the phase 3 POLARIX clinical trial (NCT03274492). The study assessed the efficacy, safety, and pharmacokinetics of the experimental combination vs the standard-of-care (SOC) regimen rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

“The POLARIX study results suggest that Polivy plus R-CHP could transform the treatment of this aggressive malignancy, and we are working with the FDA to bring this combination to newly diagnosed DLBCL patients as soon as possible,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, in a press release. “We hope it will become the new [SOC] for the first-line treatment of DLBCL, potentially reducing the need for subsequent treatments and limiting patient burden.”

Clinical meaningful improvement in progression-free survival (PFS) was shown with the polatuzumab vedotin combination compared with R-CHOP. Polatuzumab vedotin plus R-CHP achieved a 27% reduction in the risk of disease progression vs SOC. At a median follow-up of 28.2 months, the hazard ratio for the improvement in PFS shown with polatuzumab vedotin/R-CHP was 0.73 (95% CI, 0.57-0.95; P < .02).

In the international, randomized, double-blind, placebo-controlled POLARIX study, 879 patients who were 18 to 80 years of age and had CD20-positive DLBCL were included. All patients were previously untreated with a ECOG performance status of 0 to 2, an International Prognostic Index score between 2 and 5, and adequate hematologic, renal, hepatic, and cardiac function. The patients were randomly assigned 1:1 to receive either polatuzumab vedotin/RHP or R-CHOP.2

The primary end point of the study was PFS assessed by the investigator. The key secondary end point of the study included the percentage of patients with a complete response (CR), the percentage of patients who are progression free, event-free survival (EFS), overall survival (OS), disease-free survival (DFS), duration of response, time to deterioration, and quality-of-life outcomes. The study also evaluated the percentage patients with adverse events (AEs), serum concentration of polatuzumab vedotin, plasma concentration of polatuzumab vedotin conjugate, and the percentage of patient with an anti-drug antibody to polatuzumab vedotin as secondary end points.

Full results from POLARIX were published in the New England Journal of Medicine. It was reported that the 2-year investigator-assessed EFS was 75.6% (95% CI, 71.5%-79.7%) in the experimental arm vs 69.4% (95% CI, 65.0%-73.8%) in the control arm. The hazard ratio for the difference in EFS was 0.75 (95% CI, 0.58-0.96; P = .02).3

The was no significant difference in the percentage of patients who achieved a CR at the end of treatment. Specifically, the polatuzumab vedotin arm had a 78.0% CR rate compared with 74.0% in the R-CHOP arm.

Investigator-assessed DFS was improved with polatuzumab vedotin/R-CHP vs R-CHOP. The hazard ratio of relapse or death was hazard ratio for relapse or death, 0.70 (95% CI, 0.50-0.98). There was no significant difference in OS outcomes in the study. In the polatuzumab vedotin/R-CHP arm, the estimated 2-year OS was 88.7% (95% CI, 85.7%-91.6%) compared with 88.6% (95% CI, 85.6%-91.6%) in the R-CHOP arm (HR, 0.94; 95% CI, 0.65-1.37; P = .75).

For safety, outcomes were consistent with prior clinical trials. Safety was also comparable between the polatuzumab vedotin/R-CHP and R-CHOP treatment arms. Grade 3/4 AEs were observed in 57.7% of the experimental arm compared with 57.5% of the SOC arm.1 Serious AEs occurred in 34.0% vs 30.6%. Grade 5 AEs occurred in 3.0% of the polatuzumab vedotin/R-CHP arm vs 2.3% of the R-CHOP arm. AEs led to dose reduction in 9.2% of patients who received the experimental combination vs 13.0% of the those treated with R-CHOP.

The most common grade 3/4 AEs in the experimental group vs the control group were neutropenia (28.3% vs 30.8%), febrile neutropenia (13.8% vs 8.0%), and anemia (12.0% vs 8.4%), respectively.3

The POLARIX results have already led to an approval of polatuzumab vedotin and R-CHP for the treatment of adult patients with previously untreated relapsed or refractory DLBCL by the European Commission. The decision added to the approval of polatuzumab vedotin across 70 countries. The FDA plans to decide on the potential approval of polatuzumab vedotin/R-CHP for the treatment of patients with previously untreated DLBCL on April 2, 2023.1


1. FDA accepts supplemental Biologics License Application for Roche’s Polivy combination for people with previously untreated diffuse large B-cell lymphoma. News release. Roche. August 16, 2022. Accessed August 16, 2022. https://bit.ly/3CapXqy

2. A study comparing the efficacy and safety of polatuzumab vedotin with rituximab-cyclophosphamide, doxorubicin, and prednisone (R-CHP) versus rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with diffuse large b-cell lymphoma (POLARIX). Clinical trials.gov. Updated May 21, 2022. Accessed August 16, 2022. https://bit.ly/3poiuwi

3. Tilly H, Morscauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large b-cell lymphoma. N Engl J Med. 2022;386:351-363. doi:10.1056/NEJMoa2115304