Midostaurin therapy for advanced systemic mastocytosis: Mayo Clinic experience in 33 consecutive cases

Abstract

We retrospectively examined our experience with midostaurin therapy in 33 consecutive patients (median age 68 years; 58% females) with advanced systemic mastocytosis (adv-SM): aggressive SM (ASM; n = 17), SM associated with another hematologic neoplasm (SM-AHN; n = 14) and mast cell leukemia (MCL; n = 2). KITD816V mutation was detected in 84% of the patients and C findings in 91%. Eleven (33%) patients were previously treated with other cytoreductive drugs, including cladribine (n = 4) and imatinib (n = 3). Median time from diagnosis to initiation of midostaurin therapy was 2.2 months (range 0.3-41). Using modified valent criteria, overall response was 42% (53% ASM, 29% SM-AHN, 50% MCL; p = .22), all classified as being major. Responses included ≥50% reduction in bone marrow mast cells in 40% and normalization of serum tryptase in 29%, of evaluated cases. After a median follow-up of 14.6 months from initiation of midostaurin therapy, 7 (21%) deaths, 1 (3%) leukemic progression, and 18 (55%) treatment discontinuations were documented; median duration of midostaurin treatment was 7.9 months (range 0.5-123) and response duration 21.5 months (range 2.9-123).Most frequent side effect was gastrointestinal (51%) while grade 3/4 neutropenia or thrombocytopenia occurred in 12% of patients. Response to treatment was not predicted by KIT mutation (p = .67) or exposure to prior cytoreductive therapy (p = .44).Median survival was longer in midostaurin responders but not significantly (median 26.5 vs. 16 months; p = .15). Findings from the current study are broadly consistent with previously published clinical trial observations.

Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis

“…As the majority (>90%) of patients with AdvSM carry a KIT D816V mutation [11], recent therapeutic advances have focused on KIT inhibitors [12]. Treatment options for patients with AdvSM include the multikinase KIT inhibitor midostaurin, for which efficacy and safety has been reported in several clinical trials and observational studies [9,[13][14][15][16][17][18]. In addition, imatinib is a treatment option for the limited indication of ASM patients who are KIT D816V-negative or with unknown KIT mutation status [19].…”

Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management

“…The median OS for the overall cohort and MCL patients was 40 months and 18.5 months, respectively. No unexpected toxicities emerged during the longer follow up.In the retrospective Mayo Clinic study of 33 patients with advanced SM (11 pretreated—including cladribine 4, imatinib 3), the ORR using modified Valent criteria was 44% (all major responses) 106 . Responses included ≥50% reduction in BM MC in 40% and normalization of serum tryptase in 29% of evaluable cases.…”

Mast cell sarcoma: 2 Mayo Clinic cases

“…The observations from the current study and those of Matsumoto, et al 3 confirm differences in neoplastic mast cell staining pattern and KIT mutation expression between MCS (often KIT unmutated and variable expression of CD25) and SM (often expressing both KIT mutation and CD25). Treatment outcome in MCS, often consisting of surgical resection and involved‐field radiation, was poor and might warrant addition of chemotherapy, perhaps in the form of cladribine, 4 midostaurin, 5 or avapritinib 6 …”