AML-325 Prognostic Impact of RAS and C-KIT Mutations (Single vs. Multiple) in Core-Binding Factor Acute Myeloid Leukemia (CBF-AML) Treated With a Fludarabine, Cytarabine, and G-CSF (FLAG)– Based Regimen

Context: Despite a favorable prognosis, 30%–50% of patients (pts) with CBF-AML eventually relapse. Both RAS and KIT mutations have been associated with poor outcomes. Objective: We studied the prognostic impacts of RAS and KIT mutations, the number of mutations, and the impact of mutation status on the attainment of optimal PCR reductions at the end of induction and the end of treatment (EOT). Methods: Pts ≥ 18 years with de novo CBF-AML treated with a FLAG-based regimen between 2013 and 2019 were included. RAS and KIT mutations were assessed by next-generation sequencing. PCR for disease-specific transcripts was monitored at the end of C1 and at EOT. Results: Of 91 pts with CBF-AML evaluated, the median age was 52 years (range, 22–79 years), and 41 were women (45%). Inv 16 was identified in 53 pts (58%), and 38 had t (8;21). FLT3 mutation was identified in 26 pts (29%), 32 pts (35%) had RAS mutation (19 NRAS, 3 KRAS, and 10 both), and 30 pts (33%) had KIT mutation. Of 32 pts with RAS mutation, 16 (50%) had single mutation, and 16 (50%) had multiple mutations. Of 30 pts with KIT mutation, 25 pts (83%) had single mutation, and 5 pts (17%) had multiple mutations. On regression analysis examining the presence of KIT or RAS mutation and their impacts on the end of induction and EOT PCR, only KIT mutations were associated with lower odds (0.33, 95% CI 0.11–0.9) of optimal EOT response. Among mutated pts, the presence of single versus multiple mutations did not affect optimal PCR responses. At a median follow-up of 53.1 months, the median relapse-free survival (RFS) for the whole cohort was 27.7 months (range, 1.7–93.6). RAS-mutated pts had longer RFS than non-mutated pts (not reached vs. 43.78 months, p=0.02); however, KIT mutation did not affect RFS. Additionally, the number of the RAS or KIT mutations did not impact RFS. Conclusions: KIT mutation might negatively affect the attainment of optimal PCR responses at the end of FLAG-based therapy but lacks significant impacts on RFS. Single versus multiple KIT or RAS mutations do not appear to impact therapy response.