FDA Approves Polatuzumab Vedotin Plus R-CHP for Treatment-Naïve DLBCL

The FDA has granted approval to 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 approval decision comes a monthafter the FDA’s Oncologic Drugs Advisory Committee decided that the benefit/risk profile of polatuzumab vedotin plus R-CHP was favorable for patients with previously-treated DLBCL. The FDA panel saw data from the phase 3 POLARIX clinical trial (NCT03274492),showingthat the combination had a clinically meaningful improvement in progression-free survival (PFS) compared with the standard-of-care regimen, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).²These findings from POLARIX arethe basis for the approval.¹ 

“It has been nearly 20 years since a new treatment option has become available to people newly diagnosed with diffuse large B-cell lymphoma,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, in a press release. “Today’s decision from the FDA to approve [polatuzumab vedotin] in combination with R-CHP in this setting brings a much-needed new treatment option which may improve outcomes and bring other benefits to many patients with this aggressive lymphoma.”

The international, randomized, double-blind, placebo-controlled, confirmatory study included a total of 879 patients between the ages of 18 to 80 years. Patients were eligible for the study if they had CD20-positive DLBCL, were previously untreated, had 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.³

Patients in the study were randomized 1:1 to receive either the experimental polatuzumab vedotin combination or R-CHOP. The primary end point assessed was PFS, and the key secondary end points included percentage of patients with a complete response (CR), the percentage of patients who wereprogression-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 explored the percentage of patients with adverse events (AEs), serum concentration of polatuzumab vedotin, plasma concentration of polatuzumab vedotin conjugate, and the percentage of patients with an anti-drug antibody to polatuzumab vedotin as secondary end points.

According to findings published in the New England Journal of Medicine, treatment with polatuzumab vedotin plus R-CHP significantly lowered the risk of disease progression or death compared with R-CHOP (stratified HR, 0.73; 95% CI, 0.57-0.95; P=.02). At a median follow-up of 28.2 months (range, 0.1-43.4), the PFS rate was 24.3% in the polatuzumab vedotin plus R-CHP arm vs 30.5% in the R-CHOP arm.

The EFS rate was 25.5% with polatuzumab vedotin plus R-CHP vs 31.4% with R-CHOP (HR, 0.75; 95% CI, 0.58-0.96; P =.02). OS in the polatuzumab vedotin plus R-CHP was 12.0% vs 13.0% in the R-CHOP arm (HR, 0.94; 95% CI, 0.65-1.37; P =.75). In terms of DFS, the rate was 16.3% in the polatuzumab vedotin plus R-CHP vs 21.8% in the R-CHOP arm (HR, 0.70; 95% CI, 0.50-0.98). 

In terms of DFS, the rate was 16.3% in the polatuzumab vedotin plus R-CHP vs 21.8% in the R-CHOP arm (HR, 0.70; 95% CI, 0.50-0.98).

Responses were also more favorable in the polatuzumab vedotin/R-CHP vs the R-CHOP arm. The ORR was 85.5% vs 83.8%, respectively. Among patients treated with polatuzumab vedotin plus R-CHP, responses included complete responses (CRs) in 78.0% of patients, partial responses (PRs) in 7.5%, stable disease (SD) in 1.8%, and progressive disease (PD) in 5.0%. Response was notevaluated, or data was missing for 7.7% of patients in the polatuzumab vedotin plus R-CHP arm. In the R-CHOP arm, 74.0% of responses were CRs, 9.8% were PRs, 1.4% were SD, and 6.4% were PD. The remaining 8.4% of patients were either not evaluated or had missing data.

Adverse events (AEs) of any grade were observed in a significant proportion of patients in both treatment arms. The most common any-grade AEs in the polatuzumab vedotin/R-CHP group vs the R-CHOP group were peripheral neuropathy (52.9% v53.9%), nausea (41.6% v 36.8%), neutropenia (30.8% v 32.6%, and diarrhea (30.8% v 20.1%).

REFERENCES:

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 19, 2023. https://bwnews.pr/3mLgi4b

Oncologic Drugs Advisory Committee (ODAC) Meeting. FDA website. March 9, 2023. Accessed March 9, 2023. https://www.fda.gov/advisory-committees/advisory-committee-calendar/march-9-2023-meeting-oncologic-drugs-advisory-committee-meeting-announcement-03092023

Tilly H, Morchhauser F, She LH, et al. Polatuzumabvedotin in previously untreated diffuse large b-cell lymphoma. N Engl J Med. 2022; 386(4):351-363. doi:10.1056/NEJMoa2115304