Predicting the clinical course of advanced systemic mastocytosis on treatment with avapritinib or midostaurin
7 affiliations
- 1Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany
- 2Stanford University School of Medicine and Stanford Cancer Institute, Stanford, CA USA
- 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA USA
- 4Guy’s & St Thomas’ NHS Foundation Trust, London, UK
- 5Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI USA
- 6ARUP Laboratories, University of Utah, Salt Lake City, UT USA
- 7Blueprint Medicines Corporation, Cambridge, MA USA
Abstract
Advanced systemic mastocytosis (AdvSM) is driven by KIT D816V in approximately 95% of cases. Accurate assessment and prediction of clinical course and disease outcome before and during treatment with the KIT inhibitors midostaurin and avapritinib may facilitate optimization of treatment strategies. We retrospectively evaluated clinical, morphologic, laboratory, and genetic predictors of outcome in 79 midostaurin- and 176 avapritinib-treated patients. The number of mutations at baseline in SRSF2/ASXL1/EZH2 (midostaurin) and in SRSF2/RUNX1/SETBP1 (avapritinib) delineated highly predictive 3-tier risk classification systems. Treatment with avapritinib was associated with an early response of the KIT D816V variant allele frequency; a ≥10% reduction in peripheral blood at day 15 indicated improved overall survival (OS). Within 3 months of starting treatment, a ≥25% increase in alkaline phosphatase (AP) levels (AP flare) was observed in 46/47% of midostaurin/avapritinib-treated patients and was associated with longer OS. Multivariable analyses identified a ≥25% reduction in the KIT D816V allele burden (midostaurin), normalization of serum albumin levels (avapritinib), and normalization of hemoglobin and/or platelet levels (midostaurin and avapritinib) within 6 months as significant predictors for prolonged OS. In conclusion, genetic profiling, dynamic laboratory parameters, and KIT D816V monitoring improve outcome prediction in patients with AdvSM on midostaurin or avapritinib.
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BibTeX
@article{lubke2026predicting,
title = {{Predicting the clinical course of advanced systemic mastocytosis on treatment with avapritinib or midostaurin}},
author = {Johannes Lübke and Jason Gotlib and Daniel J. DeAngelo and Juliana Schwaab and Deepti H. Radia and Michael Deininger and Tracy I. George and Ilda Bidollari and Saša Dimitrijević and Javier I. Muñoz-González and Hongliang Shi and Andreas Reiter},
journal = {Leukemia},
year = {2026},
month = oct,
doi = {10.1038/s41375-026-03149-0},
url = {https://doi.org/10.1038/s41375-026-03149-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Predicting the clinical course of advanced systemic mastocytosis on treatment with avapritinib or midostaurin
AU - Johannes Lübke
AU - Jason Gotlib
AU - Daniel J. DeAngelo
AU - Juliana Schwaab
AU - Deepti H. Radia
AU - Michael Deininger
AU - Tracy I. George
AU - Ilda Bidollari
AU - Saša Dimitrijević
AU - Javier I. Muñoz-González
AU - Hongliang Shi
AU - Andreas Reiter
PY - 2026
DA - 2026/10/09
JO - Leukemia
DO - 10.1038/s41375-026-03149-0
UR - https://doi.org/10.1038/s41375-026-03149-0
AB - Advanced systemic mastocytosis (AdvSM) is driven by KIT D816V in approximately 95% of cases. Accurate assessment and prediction of clinical course and disease outcome before and during treatment with the KIT inhibitors midostaurin and avapritinib may facilitate optimization of treatment strategies. We retrospectively evaluated clinical, morphologic, laboratory, and genetic predictors of outcome in 79 midostaurin- and 176 avapritinib-treated patients. The number of mutations at baseline in SRSF2/ASXL1/EZH2 (midostaurin) and in SRSF2/RUNX1/SETBP1 (avapritinib) delineated highly predictive 3-tier risk classification systems. Treatment with avapritinib was associated with an early response of the KIT D816V variant allele frequency; a ≥10% reduction in peripheral blood at day 15 indicated improved overall survival (OS). Within 3 months of starting treatment, a ≥25% increase in alkaline phosphatase (AP) levels (AP flare) was observed in 46/47% of midostaurin/avapritinib-treated patients and was associated with longer OS. Multivariable analyses identified a ≥25% reduction in the KIT D816V allele burden (midostaurin), normalization of serum albumin levels (avapritinib), and normalization of hemoglobin and/or platelet levels (midostaurin and avapritinib) within 6 months as significant predictors for prolonged OS. In conclusion, genetic profiling, dynamic laboratory parameters, and KIT D816V monitoring improve outcome prediction in patients with AdvSM on midostaurin or avapritinib.
SN - 0887-6924
SN - 1476-5551
ER -