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Clinical and immunological effects of adding cyclophosphamide to pomalidomide-dexamethasone in relapsed-refractory multiple myeloma: The randomized MUKseven trial.

Created on 16 Jun 2026

Authors

Andrew Hall, James Croft, Katrina Walker, Kevin Boyd, Sadie Roberts, Amy Holroyd, Mamta Garg, Elsa Ferris, Gordon Cook, William E Pierceall, Anjan Thakurta, Anita Gandhi, Charlotte Pawlyn, Sarah R Brown, Martin Kaiser

Published in

British journal of haematology. Jun 16, 2026. Epub Jun 16, 2026.

Abstract

There is an ongoing need for accessible combination therapies for patients with relapsed-refractory multiple myeloma (RRMM), alongside a growing interest in understanding their immunological effects, particularly on T-cell populations. Myeloma UK (MUK) MUKseven (NCT02406222) was an academic, UK multicentre randomized controlled, open-label phase 2 trial. The planned sample size was 250 patients but recruitment was stopped early due to changes in standard of care. Between 2016 and 2018, 104 RRMM patients from 26 UK hospitals were recruited and randomized to receive cyclophosphamide, pomalidomide, and dexamethasone (CPd) or pomalidomide and dexamethasone (Pd) using minimization. Fifty-four participants in each arm were analysed. The primary end-point, progression-free survival (PFS) was not met with median 6.9 months (95% Confidence Interval (CI): 5.7-10.4) for CPd versus 4.6 months for Pd (95% CI: 3.5-7.4), although not significant; reflecting underpowering from early closure. CPd showed a higher overall response rate, and toxicity was comparable to previously reported Pd regimens. Peripheral blood T-cell analysis revealed stronger and more sustained enrichment of CD3+ T cells, HLA-DR-positive CD8+ and CD8+ effector memory cells in the CPd arm. Pretreatment CD4+ T-cell levels were identified as a prognostic PFS marker. In summary, our results demonstrate significant effects of cycloaddition to Pd on response and T-cell composition.

PMID:
42299497
Bibliographic data and abstract were imported from PubMed on 16 Jun 2026.

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