Frequency and prognostic impact of KIT and other genetic variants in indolent systemic mastocytosis

Abstract

pathogenic variants of A/R/D VAFs ‡ 30% (HR, 4.2; P 5 .02), were the best combination of independent predictors for PFS. In turn, A/R/D gene pathogenic VAF ‡ 30% was the only independent predictor for OS (HR, 51.8; P < .001) progression-free survival (PFS) and overall survival (OS). Multivariate analysis showed that serum b2-microglobulin (sb2M) levels > 2.5 mg/mL (hazard ratio [HR], 9.8; P 5 .001), together with a KIT D816V VAF ‡ 1% in bone marrow (BM) (HR, 10.1; P 5 .02) and pathogenic variants of A/R/D VAFs 30% (HR, 4.2; P 5 .02), were the best combination of independent predictors for PFS. In turn, A/R/D gene pathogenic VAF 30% was the only independent predictor for OS (HR, 51.8; P < .001). Based on these variables, 2 scoring systems were constructed for risk stratification of ISM at diagnosis with significantly different 10-year PFS (100%, 91%, 0% for scores of 0, 1, 2, respectively) and OS (100% and 50% for scores of 0 and 1) rates.