Oncology Advances: Polatuzumab Vedotin Improves Rate of Response, Reduces Risk of Death in DLBCL
Polatuzumab vedotin plus bendamustine and rituximab yielded a high complete response (CR) rate and reduced the risk of death in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) compared to bendamustine and rituximab alone, according to the GO29365 study.
The study included a randomly assigned cohort that consisted of a total of 80 patients. Patients were randomized in a 1:1 ratio to receive polatuzumab plus bendamustine and rituximab (n = 40) or bendamustine-rituximab only (n = 40).
Treatment was administered in six 21-day cycles. Intravenous polatuzumab vedotin was administered at a dose of 1.8 mg/kg on day 2 of cycle 1 and on day 1 of subsequent cycles. Bendamustine was administered intravenously at 90 mg/m2 on days 2 and 3 of cycle 1 and on days 1 and 2 of subsequent cycles and rituximab at 375 mg/m2 on day 1 of each cycle.
The primary end point of the study was CR rate at the end of treatment as assessed by an independent review committee. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS), which were analyzed using Kaplan-Meier and Cox regression methods.
The CR rate in the polatuzumab vedotin arm was 40% vs 17.5% with bendamustine-rituximab alone (P = .026). The best overall response rate (complete and partial responses [PR]; n = 25) was 63% with vs 25%, respectively. Of the 25 patients who achieved a CR or PR, 16 (64%) had response durations of ≥6 months and 12 (48%) had response durations of ≥12 months.
The median PFS was 9.5 in the polatuzumab arm vs 3.7 months in the bendamustine-rituximan only arm (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21 to 0.63; P <.001). After a median follow-up of 22.3 months, the median OS was 12.4 vs 4.7 months, respectively (HR, 0.42; 95% CI, 0.24 to 0.75; P = .002).
The most common adverse events in patients treated with polatuzumab vedotin plus bendamustine-rituximab included grade 3 to 4 neutropenia (46.2% vs 33.3% with bendamustine-rituximab alone), anemia (28.2% vs 17.9%), and thrombocytopenia (41% vs 23.1%). The 2 arms experienced similar rates of grade 3 to 4 infections (23.1% vs 20.5%). Peripheral neuropathy associated with polatuzumab vedotin occurred in 43.6% of patients, though authors noted this was of grade 1 to 2 and resolved in most patients.
Based on the results of this trial, polatuzumab vedotin was approved from the FDA in combination with bendamustine and rituximab for adult patients with relapsed/refractory DLBCL, after ≥2 prior therapies in June 2019.
Sources:
1. Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020;38(2):155-165. doi:10.1200/jco.19.00172
2. FDA Approves Polatuzumab Vedotin for Diffuse Large B-Cell Lymphoma. United States Food and Drug Administration. June 10, 2019. Accessed January 12, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-diffuse-large-b-cell-lymphoma
