BLAST: a globally applicable and molecularly versatile survival model for chronic myelomonocytic leukemia Available to Purchase

• A new clinical risk model in CMML, acronymized to BLAST, is easy to implement, globally applicable, and molecularly adaptive.

• Molecular information helps identify BLAST low- or intermediate-risk patients in whom allogeneic transplant is advised earlier than later.

We sought to develop a survival model in chronic myelomonocytic leukemia (CMML) that is primarily based on clinical variables and examine additional impact from mutations and karyotype. A total of 457 molecularly annotated patients were considered. Multivariable analysis identified circulating blasts ≥2% (1 point), leukocytes ≥13 × 10⁹/L (1 point), and severe (2 points) or moderate (1 point) anemia as preferred risk variables in developing a clinical risk stratification tool for overall survival (OS), acronymized to “BLAST”: low risk (0 points; median, 63 months); intermediate risk (1 point; median, 28 months; hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.6-3.0), and high risk (2-4 points; median, 13 months; HR, 5.4; 95% CI, 4.1-7.3); the corresponding 3/5-year OS rates were 68%/53%, 43%/18%, and 12%/1%. BLAST model performance (area under the receiver operating characteristic curve [AUC] 0.77/0.85 at 3/5 years) was shown to be comparable to that of the molecular CMML-specific prognostic scoring system (AUC 0.73/0.75) and the international prognostic scoring system-molecular (AUC 0.73/0.74). Multivariable analysis of mutations and karyotype identified PHF6^MUT and TET2^MUT as being “favorable” and DNMT3A^MUT, U2AF1^MUT, BCOR^MUT, SETBP1^MUT, ASXL1^MUT, NRAS^MUT, PTPN11^MUT, RUNX1^MUT, TP53^MUT, and adverse karyotype, “unfavorable.” Molecular information was subsequently encoded in a combined clinical-molecular risk model (BLAST-mol; AUC 0.80/0.86 at 3/5 years) that included the aforementioned BLAST clinical risk variables and a 3-tiered molecular risk score. BLAST and BLAST-mol were subsequently validated by 2 separate external cohorts. Independent risk factors for blast transformation included DNMT3A^MUT, ASXL1^MUT, PHF6^WT, leukocytes ≥13 × 10⁹/L, and ≥2% circulating or ≥10% bone marrow blasts. The current study proposes an easy-to-implement, globally applicable, and molecularly adaptive risk model for CMML.