PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenström's Macroglobulinaemia
Kothari, Jaimal Eyre, Toby Rismani, Ali Ediriwickrema, Kushani Edwards, Darren Galani, Sevasti Wilson, William Lawrie, Anthony Clifton-Hadley, Laura McCarthy, Helen
Kothari, Jaimal
Eyre, Toby
Rismani, Ali
Ediriwickrema, Kushani
Edwards, Darren
Galani, Sevasti
Wilson, William
Lawrie, Anthony
Clifton-Hadley, Laura
McCarthy, Helen
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2024-08-19
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Abstract
The 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.
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Kothari J, Eyre T, Rismani A, Ediriwickrema K, Edwards D, Galani S, Wilson W, Lawrie A, Clifton-Hadley L, McCarthy H, Collins A, Lewis D, Arulogan S, Auer R, Pratt G, de Tute R, Owen R, D'Sa S. PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenström's Macroglobulinaemia. Br J Haematol. 2024 Aug 19. doi: 10.1111/bjh.19706. Epub ahead of print.
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