According to data from 2 years of follow-up, patients with advanced systemic mastocytosis (SM) experienced durable responses with clinically meaningful benefit from the KIT D816V inhibitor, avapritinib. This report provided updated, 2-year data from the PATHFINDER study, which was presented at the SOHO 2023 Annual Meeting.

The open-label, multicenter phase 2 study ( identifier: NCT03580655) treated 107 patients with advanced SM with avapritinib, either as first- or second-line treatment. Patients with acute myeloid leukemia or high or very high-risk myelodysplastic syndrome were excluded.

The primary endpoint was objective response rate (ORR) and secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and objective disease burden measures.

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At baseline, the median age was 68 and 42% of patients were female. The Eastern Cooperative Oncology Group performance status was 0-1 among 74% of patients and 2-3 among 26%. There were 20% of patients with aggressive SM (ASM), 66% with SM with associated hematologic neoplasm (SM-AHN), and 14% with mast cell leukemia (MCL). The KIT D186V mutation was present among 96% of patients.

The most common prior treatment among the 39% of patients who had at least 1 prior systemic therapy was midostaurin at 54%, followed by cladribine at 11%, interferon at 9%, and imatinib at 5%.

The ORR of the entire study population was 73% with a median time to response of 2.3 months and a DOR not reached. The DOR at 24 months was 89%. Patients who were treatment-naïve demonstrated an ORR of 90%, whereas patients with prior treatment had an ORR of 64%. The ORR by subtype was similar, with 77% among patients with ASM, 75% with SM-AHN, and 67% with MCL.

The median PFS was not reached in all patients or in the different subtype groups. When stratified by prior treatment, the median PFS was not reached for those who had received prior therapy and was 39 months among treatment-naïve patients. The 24-month PFS for all patients was 76%, 89% for patients who were treatment-naïve, and 68% for previously-treated patients.

The median OS was not reached for all patients, SM subtype groups, or among patients with or without prior treatment. The overall 24-month OS was 79%, and 88% and 73% among treatment-naïve or previously-treated patients, respectively.

There were 88% of patients who experienced a decrease of at least 50% in bone marrow mast cell aggregates, with 70% of patients demonstrating elimination. The variant allele fraction of KIT D816V was reduced by at least 50% among 81% of patients, with less than 1% remaining among 58%.

Serum tryptase was also reduced by at least 50% among 92% of patients, with 61% of patients demonstrating levels of less than 20 ng/mL. There were 70% of patients whose spleen volume decreased by at least 35%, with 74% of spleens becoming non-palpable.

The most common grade 3-4 treatment-related adverse events were thrombocytopenia, neutropenia, and anemia. Grade 3-4 periorbital edema and peripheral edema developed among 6% and 2% of patients, respectively. Cognitive effects of any grade occurred in 24% of patients, with 3% grade 3-4 in severity. These events resolved with treatment discontinuation.

Treatment-related adverse events resulted in dose reductions or interruptions among 75% and 64% of patients, respectively, and discontinuation among 10%. There were no grade 5 events.

“After more than 2 years of follow-up of the PATHFINDER study, patients treated with avapritinib were shown to achieve sustained high response rate and low rate of progression, accompanied by reductions in objective measures of disease burden,” the authors concluded in their poster.

Disclosures: The study was supported by Blueprint Medicines Corporation. Please see the original reference for a full list of disclosures.

Gotlib J, Reiter A, Radia DH, et al. Avapritinib in patients with advanced systemic mastocytosis (AdvSM): Efficacy and safety analyses from the phase 2 PATHFINDER study with 2-year follow-up. Presented at: the Eleventh Annual Meeting of the Society of Hematologic Oncology (SOHO); September 6-9, 2023. MPN-295.