Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
MPN, Clinical Practice (Health Services and Quality), Non-Biological therapies, Chemotherapy, Chronic Myeloid Malignancies, Diseases, Therapies, Adverse Events, Myeloid Malignancies
Methods: Avapritinib was commenced in AdvSM patients with progressive disease-related symptoms and end-organ damage. The initial dose was adjusted according to tolerability and kept continuously until disease progression or unmanageable toxicity.
Results: In a cohort of 13 patients, with an age average of 68.8 years (range 57-76), 11 patients (84.6%) were diagnosed with SM-AHN; 81.8% with a concomitant diagnosis of CMML. 2 patients (15.4%) were diagnosed with ASM. All patients harbored the D816V mutation and 8 patients (61.5%) presented with additional mutations; 5 with SRSF2 and 1 with ASXL1. On application of prognostic scores; International Prognostic Scoring system for Mastocytosis (IPSM) 10 patients (76.9%) were classified as AdvSM-3/4 and Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis (MARS) 7 patients (53.8%) were stratified as high risk.
Treatment: 10 patients (76.9%) received avapritinib as a first-line regime, and 9 patients (69.2%) started at a dose of 200 mg od. Three patients were previously treated with other regimes - one patient with midostaurin, one with cladribine and one with azacytidine.
Response: Median duration of treatment was 503.7 days (range 75 - 1168 days). Baseline median blood parameters for this cohort were tryptase level of 168 ng/mL (range 91-811), alkaline phosphatase (ALP) of 437 IU/L (range 127-1235), albumin of 34.5 g/L (range 24-48) and a spleen size of 16.4 cm (range 12-26), measured by radiologically. At response evaluation, 9 patients (69.2%) had a tryptase level <20 ng/mL and 11 patients (84.6%) had normalised their ALP and albumin levels. None of the patients had a clinically enlarged spleen, with 9 patients (69.2%) having a normal spleen size on abdominal ultrasound. 8 patients had a complete pathological remission. The overall response rate (using the modified IWG-ECNM-MRT criteria) was 76.9% with a complete response (CR) or CR with partial haematologic recovery in 53.8% of patients. At the last follow-up, 3 patients (23.1%) died; 1 from SM progression, 1 from haematemesis and 1 due to progression of the AHN component but had a partial response of the SM with avapritinib.
Toxicities:10 patients (76.9%) had haematological toxicities. Bleeding was reported in 4 patients (30.8%); 3 patients with grade 1/2 (1 mucocutaneous and 2 mild gastrointestinal bleeds), and 1 fatal gastrointestinal bleed. No intracranial bleeds were reported. Fluid retention was noted in 3 patients (23.1%). Less frequent side effects noted were nausea/vomiting (2 patients) and skin/hair discoloration (1 patient). 11 patients (84.6%) needed dose reduction of avapritinib due to haematological toxicity with 8 patients (72.7%) remaining at 100 mg od. 4 patients (36.4%) had to intermittently stop treatment until haematological recovery. Avapritinib was stopped in 2 patients (15.4%) due to disease progression or unmanageable toxicity.
Conclusion: This small cohort of patients reflects the clinical heterogeneity of AdvSM and mirrors the PATHFINDER trial outcomes in ‘real world ’experience in the UK. Avapritinib as 1st line was tolerated, producing sustained clinical and pathological responses in the majority of this group of non-selected patients with AdvSM with high risk disease. Dose adjustments due to anticipated myelosuppression were made, with 72.2% of patients maintained on 100mg Avapritinib od. 2 patients with SM-AHN are referred for HSCT as a curative treatment as a result of achieving a CR with Avapritinib.
Disclosures: Lambert: Takeda: Other: Travel, Accommodations, Expenses; Kite/Gilead: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Bristol-Meyer -Squibb: Other: Other (Travel and conference fees). Tucker: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Immunovant Corps: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Amgen: Honoraria; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Psaila: Alethiomics: Consultancy, Current equity holder in private company, Honoraria, Other: Co-founder , Research Funding; Evotec: Research Funding; Galecto: Research Funding; Constellation Therapeutics: Consultancy; Blueprint Therapeutics: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau. Radia: Cogent Biosciences: Consultancy, Honoraria, Other: Steering committee member for APEX study; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Blueprint Medicines Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events, Research Funding.
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