P225 | IMPROVED OUTCOME WITH AVAPRITINIB VS MIDOSTAURIN IN SYSTEMIC MASYOCYTOSIS: A SINGLE-CENTER EXPERIENCE

BACKGROUND: Adverse systemic mastocytosis (AdvSM) includes the most aggressive SM subtypes; cKITD816V is recognized as a driver mutation in ~95% of cases. Therefore, Tyrosine Kinase Inhibitors (TKIs) represent the standard of care. Avapritinib is a new, oral TKI, highly selective for cKIT and PDGFRα, which led to impressive and unprecedented results in pivotal trials. The patients (pts) achieved 75% overall response rate (ORR) with 30% molecular remissions and the common severe adverse event (SAE) was thrombocytopenia (45%). In Italy it is employed as I line in indolent forms (ISM) with moderate/severe symptoms and from the II line onward in AdvSM. METHODS: A cohort of 17 pts were diagnosed and followed at the University Hospital in Catania, regional reference center for SM. Mutational analyses were performed by Next Generation Sequencing and survival was calculated with the Kaplan-Meier method. RESULTS: The patients displayed different subtypes: 3 ISM, 1 smoldering (SSM), 3 aggressive (ASM), 10 associated with other hematologic neoplasms (SM-AHN). Overall, 71% of them presented a D816V mutation in cKIT. However, all pts were treated with TKIs. Midostaurin was employed in 15 pts (88.2%): i. 10 (66.6%) as I line; ii. 3 (20%) as II line (previous lines: cladribine, H1/H2-blockers, imatinib); iii. 2 (13.3%) in III line (previous lines: imatinib-cladribine and steroids-cladribine). The ORR was 53.3% [8 of 17 pts achieved just a partial response(PR)] and 46.6% underwent disease progression (PD). The most reported AE was nausea. Instead, Avapritinib was employed in 6 (33.3%) pts: i. 1 as I line (SSM-CLL); ii. 4 as II (1 ISM, 1 SSM, 2 ASM); iii. 1 as III (ASM). All 3 pts with ASM were in PD after midostaurin and had a history of fractures, anaphylaxis and high tryptase levels. Avapritinib led to particularly favorable and durable outcomes (1 CR, 3 VGPR, 2 PR with complete symptoms resolution), and no SAE was registered. One patient with SSM-CLL received a TKIs combination (avapritinib+acalabrutinib) as I line with significative tryptase reduction (from 155 to 45.6 microg/L within 6 months). Avapritinib was associated with a better median PFS compared with midostaurin (NR vs 20 months, respectively) (figure 1). CONCLUSIONS: Avapritinib confirms its efficacy even in real-life, particularly with TKI-refractory ASM. Employing this drug in earlier lines will further improve the prognosis of these hard-to-treat disease.