Background and aims: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disease characterized by persistent monocytosis with dysplastic and myeloproliferative changes in the bone marrow. Hypomethylating agents have been approved for CMML in MDS trials but typically account for only ~10% of trial patients. ASTX727, an orally available fixed dose (FDC) combination of 35 mg decitabine (DEC) and 100 mg cedazuridine (CED), a cytidine deaminase inhibitor, produces comparable PK AUC exposure compared to intravenous decitabine (Garcia-Manero, et al, 2019). Here, we present outcome data from subjects with CMML enrolled in the Phase 2 and 3 studies that led to the approval of oral DEC/CED.
Methods: The studies enrolled 33 subjects who were candidates for parenteral decitabine. Clinical endpoints were best response according to International Working Group (IWG) 2006 response criteria, transfusion independence for at least 8 or 16 consecutive weeks, leukemia free survival, overall survival, and safety.
Results: Seven patients (21.2%) had Complete Responses (CR), 14 (42.4%) had marrow CR (mCR), including 5 (15.2%) with hematologic improvement (HI); Overall response rate (ORR) [CR + PR+ mCR + HI] was 75.8%. 63.6% of those dependent on red blood cell transfusions at baseline became transfusion independent for at least 8 weeks and 45.5% for 16 weeks. Median LFS was 28.3 months and median OS was 35.7 months. Safety profile is consistent with decitabine, with most grade 3 or higher events related to myelosuppression.
Conclusion: DEC/CED has a well-tolerated safety profile with clinical benefit in CMML patients.