In GO29365, primary analysis showed significantly higher independent review committee (IRC) assessed complete response rates (CRR) at end of treatment with Pola-BR versus BR (40.0% v 17.5%; P = 0.026). After a median follow up of 27 months, overall survival (OS) was significantly improved in the Pola-BR arm, with risk of death reduced by 58% (HR: 0.42; 95% CI, 0.24 to 0.75; P = 0.002) and a longer median OS with Pola-BR (12.4 months; 95% CI, 9.0 to not evaluable) compared with BR alone (4.7 months; 95% CI, 3.7 to 8.3 months).r
Longer term follow up was recently published and the benefit of Pola-BR versus BR persisted in the randomised arms (median PFS: 9.2 vs 3.7 months, HR: 0.42; 95% CI, 0.25 to 0.71; median OS: 12.4 vs 4.7 months, HR: 0.42; 95% CI, 0.24 to 0.72). Including the later extension cohort (total of 151 patients inclusive), the IRC-assessed objective response rate was 41.5% and CR rate was 38.7%; the median IRC-assessed PFS and OS were 6.6 months and 12.5 months, respectively.r
Summary of Efficacy Outcomes
(A) Progression-free survival by independent review committee. (B) Progression-free survival by investigator. (C) Overall survival of polatuzumab vedotin combined with bendamustine-obinutuzumab (pola-BR) compared with bendamustine-rituximab (BR). (D) Forest plot of overall survival according to clinical and biologic characteristics.
© JCO 2019
However, upon submission to the Pharmaceutical Benefits Advisory Committee for PBS listing, concerns over the validity of the GO29365 study results arose. These were due to differences between the control arm and the intervention arm, where age (71 vs. 67), rate of IPI >3 (42.5% vs. 22.5%), and disease bulk (37.5% vs. 25%) appeared to consign the control arm to perform poorly. The CRR for the control arm was closer to the lower end of historical CRR for BR used in the relapsed setting, ranging from 15.3% (Vacirca et al)r to 37.3% (Ohmachi et al)r. As a result, PBS listing for polatuzumab vedotin was not granted, thereby limiting its use in the Australian context.
In the P-DRIVE study, the overall response rate at end-of-treatment (EOT) by modified Lugano response criteria based on PET-CT was 42.9% (95% CI, 26.3 to 60.7), with a CR achieved in 34.3% (95% CI, 19.1 to 52.2). At a median follow-up of 5.4 months, median duration of response (DOR), progression free survival (PFS), and event-free survival (EFS) were 6.6 months, 5.2 months, and 5.1 months, respectively.r The lower limit of the 95% CI for P-DRIVE (19.1%) was higher than that of the BR arm of GO29365 (17.5%), and as such the trial met its primary objective.
Progression-free survival and overall survival (ITT population)
(A) Progression-free survival by investigator based on PET-CT or CT.. (B) Overall survival. ITT, intention-to-treat; OS, overall survival; PET-CT, positron emission tomography–computed tomography; pola + BR, polatuzumab vedotin + bendamustine + rituximab; PFS, progression-free survival.
© Cancer Sci 2021
In the retrospective analysis of polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas, Liebers et alr demonstrated a best overall response rate of 48.1%. The 6-month progression-free survival and overall survival (OS) rates were 27.7% and 49.6%, respectively. In the bridging cohort, 51.2% of patients could be successfully bridged with polatuzumab vedotin to the intended CAR T-cell therapy. The combination of polatuzumab vedotin bridging and successful CAR T-cell therapy resulted in an impressive 6-month OS of 77.9%.
Outcome of patients in the bridging cohort
(A) Actual treatment of patients intended for CAR T-cell therapy and (B) overall survival of patients who received the intended CAR T-cell therapy after polatuzumab vedotin (pola) bridging. (C-D) Intent-to-treat-analysis with progression-free survival and overall survival of complete bridging cohort intended for CAR T-cell therapy. Survival times were calculated from the initiation of pola treatment. For the estimation of progression-free survival, data were only assessed in the efficacy-evaluable population. Three patients had no response evaluation and were excluded from the progression-free survival estimation.
© Blood Advances 2021