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

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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Publication Details

Journal
British Journal of Haematology
Published
2024-08-19
DOI
https://doi.org/10.1111/bjh.19706
Citations
4
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
1.75

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article

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

Rebecca Auer, Shirley D’Sa, Ali Rismani, William Wilson et al.
4 citations
British Journal of Haematology
Chronic Lymphocytic Leukemia Research
1.75
article

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

Rebecca Auer, Shirley D’Sa, Ali Rismani, William Wilson, Sevasti Galani, Laura Clifton‐Hadley, Guy Pratt, Toby A. Eyre, Roger G. Owen, Kushani Ediriwickrema, Helen O. McCarthy, Ruth de Tute, Anthony Lawrie, David Lewis, Jaimal Kothari, Angela Collins, Darren Edwards, Suzanne Arulogan
article en
4 citations

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.

British Journal of HaematologyVol. 205(6)
Dorset HealthCare University NHS Foundation Trust (GB), University College Hospital (GB), Leeds General Infirmary (GB), St Bartholomew's Hospital (GB), University Hospitals Birmingham NHS Foundation Trust (GB), St Thomas' Hospital (GB), Guy's and St Thomas' NHS Foundation Trust (GB), Leeds Teaching Hospitals NHS Trust (GB), Norfolk and Norwich University Hospital (GB), Cancer Research UK (GB), Derriford Hospital (GB), London Cancer (GB), St. Thomas Hospital (CA), Oxford University Hospitals NHS Trust (GB), CRUK Lung Cancer Centre of Excellence (GB), University Hospitals Dorset NHS Foundation Trust, University College London (GB)
Merck Sharp and Dohme
Good health and well-being
Openalex Percentile: Top 15%
Chronic Lymphocytic Leukemia Research
1.75
DOIOpen Access PDFOpenAlex
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