Hypomethylating agents in the treatment of chronic myelomonocytic leukemia: a meta-analysis and systematic review

Abstract

Objectives: The present meta-analysis was performed to evaluate the efficacy, toxicities of both hypomethylating agents (decitabine and azaciticine) in the treatment of CMML patients. Methods: All available cohort studies of patients with CMML treated with decitabine and azacitidine were identified. The primary endpoints of this meta-analysis were response to hypomethylating agents. Pooled estimates of treatment response and drug-related adverse events were calculated using fixed or random effect models. Results: Fourteen studies with 600 CMML patients (decitabine: n=196; azacitidine: n=404) were identified and included for meta-analysis. HMAs yielded a pooled ORR estimate of 43% (95% CI: 36%-50%) in patients with CMML. Patients received either azacitidine or decitabine exhibited comparable incidence of ORR (43% vs. 45%, P=0.810), while significantly higher incidence of mCR was observed in patients treated with decitabine (23% vs. 10%, P=0.000). Decitabine treatment was also associated with higher incidence of transfusion independence (42% vs. 20%, P=0.044). Both HMAs led to objective hematologic or non-hematologic AEs (27%-43%), while dosage modification/delay were more frequent in patients treated with azacitidine (81% vs. 67%, P=0.021). Conclusion: This current study may provide preliminary data in evaluating the efficacy and safety of HMAs in patients with CMML. Decitabine and azacitidine are comparable effective and safe in treating CMML. However, it is necessary to point out that any comparison of decitabine and azacitidine with respect to clinical outcomes can only be done in the context of a randomized controlled trial.

Definitions, Biology, and Current Therapeutic Landscape of Myelodysplastic/Myeloproliferative Neoplasms

“…Since then, clinical trials of HMA in CMML-specific populations have been performed. A meta-analysis of fourteen pooled studies, including 600 patients with CMML, identified an estimated ORR that was very similar between the DAC and AZA groups, but with CR rates slightly higher in patients treated with DAC (23% in DAC vs. 10% in AZA) [41]. Drummond et al conducted a multicenter phase II study of AZA in 32 CMML patients, identifying an ORR of 20% with a CR of 7% [42].…”

3055 – Multi-Omics Reveals Azacitidine Partially Restores the Hematopoiesis-Supportive Functions in Mesenchymal Stromal Cells From Patients With Chronic Myelomonocytic Leukemia

“…The two FDA-approved de-methylating compounds for CMML, azacitidine (AZA) and decitabine (DEC) were initially designed to restore the disordered epigenetics in malignant HSPCs, which were thought to be disease-promoting consequences of genetic lesions involving epigenetics (2). However, demonstrated by the limited inhibitory effect on malignant clones in patients, HMAs may not produce e cacies prominently through the direct anti-tumor effect (7)(8)(9)(10). Those post-HMA therapeutic responses (e.g., hematological improvement) (11) are more likely attributed to the selective promotion of residual healthy hematopoiesis in the bone marrow.…”