PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenström's Macroglobulinaemia

Abstract

SummaryThe optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi‐centre, phase II, single‐arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post‐CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi. A significant proportion was identified as genomically high risk with BTKC481, CXCR4 and MYD88 L265P wild‐type aberrations. Twenty‐four‐week overall response rate was 50% (60% CI 39.3%–60.7%), and median duration of response was 11.6 months (IQR: 6.3–17). The median progression‐free survival was 13.6 months (95% CI 3–19.8), and the median overall survival (OS) was not reached. Treatment was well tolerated, with minimal numbers of immune‐mediated AEs typically seen with checkpoint inhibitors. PembroWM is the first study to evaluate the feasibility of PD‐1 axis modulation in WM and has shown that in combination with Rituximab the combination is safe and deliverable.