PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenstrom's Macroglobulinaemia.
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All Authors
Kothari, J.
Eyre, T.
Rismani, A.
Ediriwickrema, K.
Edwards, D.
Galani, S.
Wilson, W.
Lawrie, A.
Clifton-Hadley, L.
McCarthy, H.
LTHT Author
de Tute, Ruth
Owen, Roger
Owen, Roger
LTHT Department
Haematology
Haematological Malignancy Diagnostic Service
Haematological Malignancy Diagnostic Service
Non Medic
Clinical Scientist
Publication Date
2024
Item Type
Clinical Trial, Phase II
Journal Article
Multicenter Study
Journal Article
Multicenter Study
Language
Subject
Subject Headings
Abstract
The optimal therapeutic approach for relapsed/refractory (R/R) Waldenstrom'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.
Journal
British Journal of Haematology