Real-world clinical characteristics and outcomes of systemic mastocytosis (SM) patients (Pts) in the era of targeted treatments (Txs): A single-center cohort analysis.

Abstract

e18588 Background: SM is a rare neoplasm characterized by abnormal mast cell proliferation, driven by a mutation in KIT D816V in >90% of pts. SM encompasses a spectrum of disease including indolent SM (ISM), aggressive SM (ASM), mast cell leukemia (MCL), SM with associate neoplasm (SM-AHN). Limited data exist on real-world outcomes of SM pts in the era of targeted txs. Methods: This is an IRB-approved, retrospective study of SM pts ≥18 years. Demographic, clinical, txs, and outcome characteristics were collected through 1/1/2025. Differences among SM subtypes were tested by Fisher's exact and Kruskal-Wallis rank sum tests for categorical and continuous variables respectively. Results: 68 pts had SM. Demographic characteristics are in Table 1. There was no significant difference aside from age. ISM pts were more likely to have normal bone mineral density (56%) than ASM or SM-AHN pts (0%, 25%) (p = 0.046). CMML 64%, MDS 27% and smoldering myeloma 9.1% were AHNs. ISM pts reported symptoms (PROs) were rash 76%, diarrhea 41%, abdominal pain 26% and fatigue 26%. ASM PROs were rash 64%, abdominal pain 27% and fatigue 27%. SM-AHN PROs were fatigue 82%, rash 55%, and abdominal pain/bloating 36%. Fatigue was more common with SM-AHN p=0.003. 89% ISM pts were on active surveillance (AS) for first line (1L) tx, and 87% were on avapritinib (ava) for 2L tx. Time to ava start was 117 months. The most common doses of ava were 25mg/day and 50mg/day. With ASM pts, 45% were on ava, 27% AS, and 9.1% each for imatinib, midostaurin (mido) and other for 1L. Most common ava doses were 200mg, 100mg and 50mg. For SM-AHN pts 1L tx was ava 30%, other 30%, mido 20%, AS 10%, imatinib 10%. 60% of pts in 2L were on ava. The most common doses of ava were 50mg and 200mg. With a median follow up of 43 months (m), the study population overall survival (OS) was not reached (NR). OS was NR for ISM or ASM pts. OS for ASM pts on 1L ava and mido were NR. OS for SM-AHN was 35m. OS for 1L ava was 28m; OS for 1L mido was 19m. 45% of SM-AHN pts had passed, with 1 treatment-related death, 2 deaths due to SM and 2 deaths due to other cause. There was a statistically significant difference between ISM/ASM and SM-AHN OS, p <0.0001. Conclusions: This real-world study highlights the heterogeneity in SM pts. OS was NR for ISM consistent with prior data. OS for ASM pts was NR; previously OS was reported at 3.5 years. SM-AHN pts had improved OS at 35m versus 24m reported previously. Targeted txs, particularly ava, demonstrate promising outcomes. Characteristic Total PopulationN = 68 ISMN = 46 ASMN = 11 SM-AHNN = 11 P Value Median Age yrs (IQR) 48 (39, 62) 42 (35, 53) 56 (50, 68) 74 (64, 77) <0.001 Female N (%) 43 (63) 33 (72) 6 (55) 4 (36) 0.073 White N (%) 58 (85) 39 (85) 9 (82) 10 (91) 0.4 Non-Hispanic N (%) 61 (90) 40 (87) 10 (91) 11 (100) >0.9 Median Tryptase ng/mL (IQR) 39 (21, 122) 24 (15, 42) 154 (96, 306) 179 (119, 242) <0.001 CKIT D816V Mutated N (%) 56 (82) 37 (80) 9 (82) 10 (91) >0.9