Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

SIMPLE SUMMARY: Chronic myelomonocytic leukemia (CMML) is an infrequent disease with poor prognosis and risk of progression into acute myeloid leukemia (AML). Stem cell transplantation (alloSCT) is the only potentially curative option. New targeted drugs (NTDs) directed at specific gene mutations are useful in AML, but little is known about how CMML progresses to AML and if these drugs are effective in CMML. In our study, 38% of patients received hypomethylating agents but less than half of them responded. Six patients received NTDs and responded well. AlloSCT was possible in only 10% of patients. Progression to AML occurred in 25% of patients, and there were changes in their gene mutations between the time of diagnosis and the time of progression. Although prognosis is poor in CMML, analyzing gene mutations can help to better stratify the risk of each patient and to identify potentially effective NTDs for each patient. ABSTRACT: Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy.