Efficacy and safety of oral decitabine/cedazuridine in the chronic myelomonocytic leukaemia subpopulations from phase 2 and 3 studies.

DNA methyltransferase inhibitors (DNMTis) are commonly used in treating chronic myelomonocytic leukaemia (CMML); however, data from prospective studies of DNMTis in CMML are limited. The present analysis evaluated the efficacy, safety and pharmacodynamics of the oral DNMTi decitabine/cedazuridine in the subset of patients with CMML from the phase 2 and 3 trials, which led to the approval of this agent for myelodysplastic syndromes and CMML in the United States and Canada. Potential prognostic factors also were analysed. In all, 34 patients with CMML were screened and 33 were treated. Most patients (76% [n = 25]) had myelodysplastic type-CMML and 77% (n = 24/31 with DNA available for sequencing) had intermediate-2 or high-risk disease noted by CMML-specific prognostic scoring systems. The overall response rate was 76%, with 21% (n = 7) of patients achieving a complete response. Nearly half of the 11 patients who were red blood cell-transfusion dependent at baseline (46%) attained transfusion independence for ≥12 weeks, which was associated with survival. Median overall and transformation-free survival were 35.7 and 28.3 months, respectively, and the safety profile was similar to that previously reported for decitabine. This analysis described the use of decitabine/cedazuridine in CMML from consecutive, prospective, randomised trials and illustrated a median survival of nearly 3 years.