Genetic and laboratory markers predict survival in treated advanced systemic mastocytosis

A retrospective study published in Leukemia assessed predictors of clinical outcomes in advanced systemic mastocytosis, which is driven by KIT D816V in approximately 95% of cases. Researchers evaluated clinical, morphologic, laboratory, and genetic parameters in 79 patients receiving midostaurin and 176 receiving avapritinib, focusing on associations with overall survival.

Baseline mutation counts in SRSF2/ASXL1/EZH2 for midostaurin and SRSF2/RUNX1/SETBP1 for avapritinib defined treatment-specific, three-tier risk classifications. Among avapritinib-treated patients, a ≥10% reduction in peripheral-blood KIT D816V variant allele frequency by day 15 was associated with improved survival. An alkaline phosphatase increase of ≥25% within three months occurred in 46% and 47% of midostaurin- and avapritinib-treated patients, respectively, and was associated with longer survival.

Multivariable analyses identified additional favorable predictors within six months: a ≥25% reduction in KIT D816V allele burden with midostaurin, serum albumin normalization with avapritinib, and normalization of hemoglobin and/or platelet levels with either treatment. These findings suggest that genetic profiling and serial molecular and laboratory monitoring may support prognostic assessment. However, the retrospective associations do not establish that changing treatment based on these markers improves outcomes. The supplied abstract does not report survival effect sizes or external validation of the risk classifications.