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Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents
Ana Alfonso1, Guillermo Montalban-Bravo1, Koichi Takahashi1
1Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
Insights
Hypomethylating agents (HMA) show effectiveness in treating chronic myelomonocytic leukemia (CMML), with decitabine yielding higher complete response rates than azacitidine. Further research is needed for improved CMML therapies.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm.
- Hypomethylating agents (HMA) are standard treatment, but their impact on CMML natural history requires further understanding.
- Lack of CMML-specific clinical trials necessitates retrospective analyses.
Purpose of the Study:
- To evaluate the efficacy and outcomes of hypomethylating agents (HMA) in a large cohort of CMML patients.
- To identify prognostic factors influencing overall survival (OS) and response to HMA therapy.
- To compare outcomes between different HMA treatments and assess HMA failure patterns.
Main Methods:
- Retrospective analysis of 151 CMML patients treated with HMA (azacitidine, decitabine, or combinations).
- Assessment of overall response rate (ORR), complete response (CR), overall survival (OS), and event-free survival (EFS).
- Multivariate analysis to identify predictors of better OS and comparison of CR rates between azacitidine and decitabine.
Main Results:
- Overall response rate (ORR) was 75% with 41% achieving complete response (CR). Median OS was 24 months.
- Decitabine showed a significantly higher CR rate (58.3%) compared to azacitidine (20.6%).
- HMA failure occurred in 50% of patients, with poor outcomes post-failure; 35% transformed to acute myeloid leukemia (AML).
Conclusions:
- Hypomethylating agents (HMA) are effective in CMML, demonstrating significant response rates and survival benefits.
- Decitabine may offer superior complete response rates compared to azacitidine in CMML.
- New therapeutic strategies and agents are crucial for improving outcomes in CMML, particularly after HMA failure.
Abstract:
Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML-specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n = 151) treated with HMA. Mean age at diagnosis was 69 years (range 50-88). According to the CMML-specific prognostic scoring system (CPSS): 17 (15%) were low-risk, 45 (39%) intermediate-1 risk, 42 (36%) intermediate-2, and 12 (10%) high-risk. 35 (23%) patients received single agent azacitidine, 73 (48%) single agent decitabine, and 43 (29%) combinations. With a median follow-up of 17 months, overall response rate (ORR) was 75%, with 41% achieving complete response (CR). Median overall survival (OS) was 24 months (95%CI: 20-28) and event-free survival 14 months (95%CI: 11-17). By multivariate analysis, age < 70 years, higher levels of hemoglobin, absence of blast in peripheral blood and lower CPSS cytogenetic risk predicted for better OS. CR was significantly higher in those patients treated with decitabine (58.3%) when compared with azacitidine (20.6%) (P < .001). 13 patients (9%) received allo-SCT after a median of 4 cycles of HMA. 66 patients (50%) had HMA failure: 26 primary (34%) and 50 secondary (66%), including 35 (46%) that transformed to AML. Outcomes after HMA failure were poor with OS of 7 months (95%CI: 3-12). In conclusion, HMA are effective in CMML but new agents and combinations are needed. This data could be a benchmark for further drug development in CMML.
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