Multicenter randomized phase 2 trial of adding cyclophosphamide to pomalidomide-dexamethasone in RRMM

There is an ongoing need for accessible combination therapies for patients with relapsed-refractory multiple myeloma (RRMM). The multicenter myeloma UK (MUK) MUKseven trial evaluated addition of cyclophosphamide (C) to pomalidomide and dexamethasone (Pd) for RRMM. The planned sample size was 250 patients, but recruitment was stopped early due to changes in standard of care. Between 2016 and 2018, RRMM patients from 26 hospitals were randomized to CPd or PD. Fifty-four patients in each arm were analyzed. The primary endpoint, progression-free survival (PFS), was not met with median 6.9 months (95% CI 5.7-10.4) for CPd versus 4.6 months (3.5-7.4) for Pd, 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. The authors conclude that these results demonstrate significant effects of addition of C to Pd on response and T-cell composition in RRMM.