MPN-352 Clinicopathologic and Molecular Correlates of Organ Damage Across the Spectrum of Advanced Systemic Mastocytosis.

Abstract

Advanced SM (AdvSM) comprises 3 subtypes: aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). The patterns of organ damage, which have been defined by WHO, IWG, and modified IWG (mIWG) criteria, across the spectrum of AdvSM have not been well characterized. 1) To describe the distribution of organ damage in AdvSM patients (pts) at initial presentation or at the time of trial enrollment; 2) To evaluate clinicopathologic and molecular correlates of organ damage. Observational study of adults with AdvSM. Tertiary referral center. Our cohort included 240 AdvSM pts: 66 from the Stanford MPN registry and 174 from the phase I EXPLORER and phase II PATHFINDER studies of avapritinib in AdvSM. None. Hematologic and non-hematologic organ damage as defined by WHO, IWG, and mIWG criteria. Thirty-seven pts (15%) had ASM, 165 (69%) had SM-AHN, and 38 (16%) had MCL. Pts with MCL had the highest transfusion requirement and the largest liver and spleen volumes by imaging. In multivariate analyses comparing SM-AHN to ASM/MCL, SM-AHN pts had higher absolute neutrophil and monocyte counts and presence of SRSF2, ASXL1, or RUNX1 (S/A/R) mutations. ASM/MCL pts had higher tryptase levels and bone marrow mast cell burden. Compared to midostaurin-naïve pts, those who had received midostaurin had a greater bone marrow mast cell burden (P=0.06) but less frequently met WHO liver (P<0.001) and WHO malabsorption (P<0.001) criteria. Compared to pts with KIT D816V only, pts with ≥1 S/A/R mutations had lower median hemoglobin (P=0.02) and platelet count (P=0.02) and higher direct bilirubin (P=0.02), alkaline phosphatase (P=0.03), and spleen volume (P=0.06). They exhibited more WHO-defined cytopenias (P=0.007) and were more likely to meet WHO hypersplenism criteria (P=0.03). In AdvSM, patterns of organ damage reflect disease subtype, prior therapy, and mutation profile. These data can help inform enrollment of AdvSM pts into clinical trials that currently require ≥1 organ damage findings. Grant Acknowledgments: ASH HONORS Award, NIH grant P30CA124435.