Efficacy and Safety of Hypomethylating Agents in Chronic Myelomonocytic Leukemia: A Single-Arm Meta-analysis

Abstract

Background Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm with features of the myelodysplastic syndromes (MDSs) and myeloproliferative neoplasm presenting with peripheral blood monocytosis and an inherent risk for transformation to acute myeloid leukemia, while the abnormal DNA methylation plays a critical role in the pathogenesis of MDS, which is a disease of disordered differentiation. Recently, with the rapid development of molecular biology, hypomethylating agents (HMAs) for the treatment of MDS has gradually become a research focus. The objective of this study was to evaluate the benefits and risks of HMAs for patients with CMML. Materials and Methods PubMed, Embase, the Cochrane Library, and three Chinese databases were searched for studies published before November 2020 that used HMAs in CMML. Results The pooled objective response rate (ORR), complete response (CR), and partial response (PR) were 50.0, 21.0, and 2.0%, respectively. The proportion of patients with minor response (MR) was significantly higher for decitabine (DAC) than for azacitidine (AZA). There was no significant difference in hematologic improvement, ORR, CR, and PR rates between the DAC and AZA groups. Hematological toxicity included neutropenia grade 3/4 (14.0%), anemia grade 3/4 (17.0%), and thrombocytopenia grade 3/4 (22.0%). Conclusion This study showed that HMAs were effective and safe in the treatment of CMML, but large multicenter study would be needed to confirm the efficacy of HMAs for the treatment of CMML with different risk level and genetic abnormality, to support individualization treatment theoretically.

Keywords: azacitidine; chronic myelomonocytic leukemia; decitabine; hypomethylating agents; meta-analysis; myelodysplastic syndromes; single-arm.

Fig. 1

Study selection process.

Fig. 2

Pooled results of response in total. ( A ) Pooled results of ORR in total was 50% (95% CI, 38–62%, I ²  = 87.08%). ( B ) The pooled CR rate after treatment with HMAs regimen was 21% (95% CI, 13–29%, I ²  = 80.22%). ( C ) Pooled results of PR in total was 2% (95% CI, 0–5%, I ²  = 55.04%). ( D ) Pooled results of MR in total was 6% (95% CI, 1–14%, I ²  = 87.20%). (E) Pooled results of HI in total was 9% (95% CI, 4–16%, I ²  = 80.73%). CI, confidence interval; CR, complete response; HI, hematologic improvement; HMAs, hypomethylating agents; ORR, objective response rate; MR, minor response; PR, partial response.

Fig. 3

Pooled results of tumor response in the AZA group. ( A ) Pooled results of ORR in the AZA group was 45% (95% CI, 40–51%, I ²  = 40.27%). ( B ) The pooled CR rate after treatment with the AZA agents was 16% (95% CI, 10–24%, I ²  = 51.35%). ( C ) Pooled results of PR in the AZA group was 2% (95% CI, 1–5%, I ²  = 43.75%). ( D ) Pooled results of MR in the AZA group was 3% (95% CI, 0–11%, I ²  = 78.20%). ( E ) Pooled results of HI in the AZA group was 10% (95% CI, 3–20%, I ²  = 79.29%). AZA, azacitidine; CI, confidence interval; CR, complete response; HI, hematologic improvement; ORR, objective response rate; MR, minor response; PR, partial response.

Fig. 4

Pooled results of tumor response in the DAC group. ( A ) Pooled results of ORR in the DAC group was 46% (95% CI, 38–54%, I ²  = 42.92%). ( B ) The pooled CR rate after treatment with the DAC agents was 20% (95% CI, 7–39%, I ²  = 82.89%). ( C ) Pooled results of PR in the DAC group was 2% (95% CI, 0–11%, I ²  = 74.34%). ( D ) Pooled results of MR in the DAC group was 8% (95% CI, 0–27%, I ²  = 88.30%). ( E ) Pooled results of HI in the DAC group was 7% (95% CI, 0–21%, I ²  = 82.59%). CI, confidence interval; CR, complete response; DAC, decitabine; HI, hematologic improvement; ORR, objective response rate; MR, minor response; PR, partial response.

Fig. 5

Pooled results of tumor response in the CMML-1 group. ( A ) Pooled results of ORR in the CMML-1 group was 47.0% (95% CI, 36.0–58.0%, I ²  = 0.00%). ( B ) The pooled CR rate in the CMML-1 group was 21.0% (95% CI, 11.0–33.0%, I ²  = 38.20%). ( C ) Pooled results of PR in the CMML-1 group was 2.0% (95% CI, 0.0–15.0%, I ²  = 53.99%). ( D ) Pooled results of MR in the CMML-1 group was 4.0% (95% CI, 0.0–13.0%, I ²  = 42.54%). ( E ) Pooled results of HI in the CMML-1 group was 6.0% (95% CI, 0.0–15.0%, I ²  = 0.00%). ( F ) Pooled results of PD in the CMML-1 group was 15.0% (95% CI, 6.0–27.0%, I ²  = 8.83%). CI, confidence interval; CMML, chronic myelomonocytic leukemia; CR, complete response; HI, hematologic improvement; ORR, objective response rate; MR, minor response; PD, disease progression; PR, partial response.