ASSESSMENT OF THE IPSS-M IN CHRONIC MYELOMONOCYTIC LEUKEMIA

Area of Science:

• Hematology
• Oncology
• Molecular Diagnostics

Background:

• Prognostication in chronic myelomonocytic leukemia (CMML) is complex due to disease heterogeneity.
• Existing prognostic models may not fully capture the molecular complexity of CMML.
• Accurate risk stratification is crucial for guiding clinical decision-making and therapeutic strategies.

Purpose of the Study:

• To evaluate the prognostic utility of the International Prognostic Scoring System-Molecular (IPSS-M) in CMML.
• To assess the applicability of IPSS-M across myelodysplastic (MD-CMML) and myeloproliferative (MP-CMML) subsets.
• To compare the performance of IPSS-M with other prognostic scores like CPSS-Mol and iCPSS.

Main Methods:

• Multicenter, retrospective study of 511 CMML patients.
• Collection of clinical, cytogenetic, and molecular data at diagnosis, including targeted next-generation sequencing (NGS).
• Stratification of patients using IPSS-M, CPSS-Mol, and iCPSS, with analysis of overall survival (OS) and acute myeloid leukemia (AML) progression.

Main Results:

• IPSS-M effectively stratified CMML patients into distinct risk groups for OS and AML progression.
• An adapted four-tier IPSS-M model demonstrated strong discrimination (c-index 0.678 for OS, 0.628 for AML progression).
• The adapted IPSS-M maintained prognostic performance in both MD-CMML and MP-CMML subsets, outperforming CPSS-Mol and showing comparability with iCPSS.

Conclusions:

• An adapted IPSS-M is applicable to CMML, extending its utility beyond myelodysplastic syndromes.
• IPSS-M can aid in guiding clinical decisions and therapeutic strategies for CMML patients.
• The study provides external validation for the iCPSS in a well-characterized CMML cohort, reinforcing its clinical utility.