Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data

Abstract

Polatuzumab vedotin plus bendamustine and rituximab (pola + BR) received regulatory approvals for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) based on primary results from the randomized arms of the GO29365 study. After the randomized phase, 106 additional patients received pola + BR in a single-arm extension cohort. We report updated results from the randomized arms and results of the extension cohort. In this phase 1b/2 study, patients with R/R DLBCL who were transplant ineligible received up to six 21-day cycles of pola + BR or BR. The primary end point of the randomized arms was the complete response (CR) rate at end of treatment. Primary objectives of the extension cohort were safety, pharmacokinetic profile, and efficacy of pola + BR. As of 7 July 2020, a total of 192 patients with R/R DLBCL were enrolled in the pola + BR cohort (n = 152 [safety run-in, n = 6; randomized, n = 40; extension cohort, n = 106]) or the BR cohort (n = 40). Significant survival benefit with pola + BR vs BR persisted in the randomized arms (median progression-free survival, 9.2 vs 3.7 months [hazard ratio, 0.39; 95% confidence interval, 0.23-0.66]; median overall survival, 12.4 vs 4.7 months [hazard ratio, 0.42; 95% confidence interval, 0.24-0.72]). In the extension cohort, the independent review committee-assessed objective response rate was 41.5%, and the CR rate was 38.7%; median independent review committee-assessed progression-free survival and overall survival were 6.6 months and 12.5 months, respectively. No new safety signals with pola + BR were identified. Pola + BR is an effective treatment option for patients with R/R DLBCL, with a well-characterized and manageable safety profile. This trial was registered at www.clinicaltrials.gov as #NCT02257567.

Graphical abstract

Figure 1.

GO29365 study design. Shown are the treatment arms from GO29365 in which patients with R/R DLBCL were assigned to receive pola + BR or BR alone.

Figure 2.

Kaplan-Meier curves of survival. IRC-assessed PFS in randomized arms (A), IRC-assessed PFS in the extension cohort (B), OS in randomized arms (C), OS in the extension cohort (D). Analyses performed in the efficacy-evaluable population.

Figure 3.

Subgroup analyses. IRC-assessed BOR (A-C), IRC-assessed PFS (D), OS (E). *Refractory to last prior treatment. BOR, best objective response; CR, complete response; NE, not evaluable; OS, overall survival; PFS, progression-free survival; PR, partial response; 2L, patients had received one prior line of therapy before treatment with Pola + BR; 3L+ patients had received two or more prior lines of therapy before treatment with Pola + BR.