DP083 | THE IMPACT OF FLT3-TKD MUTATION IN NPM1-MUTATED ACUTE MYELOID LEUKEMIA PATIENTS: A RETROSPECTIVE SUBANALYSIS OF A LARGE MULTICENTRIC ITALIAN COHORT

According to the current European Leukemia Network guidelines (ELN 2022), FLT3-TKD mutation is no longer included in the risk classification and NPM1mut FLT3-TKDmut AML patients (pts) without high risk cytogenetics are in the favorable-risk group. The aim of the study was to evaluate, in a real-life setting, the impact of FLT3-TKDmut in NPM1mut AML pts. We retrospectively analysed 327 pts with NPM1mut FLT3mut AML treated with intensive chemotherapy (CT) from Jan 2017 to Dec 2023 in 24 Italian Centers. Measurable Residual Disease (MRD) was evaluated in RT-PCR, after 2 CT cycles (2CT MRD) and at the end of consolidation CT (EoC MRD). MRD negativity (MRD-) was defined by a reduction of MRD ≥4 Log from diagnosis, MRD positivity (MRD+) when <4 Log. Median age was 58 years (range 18–80), 93,5% had a de novo AML, 62 (19%) with FLT3-TKDmut, 265 (81%) FLT3-ITDmut. The presence of FLT3-TKDmut didn’t show a significant better prognosis, compared to NPM1mutFLT3-ITDmut AML (3y OS 66,3% vs 54,2% and 3y EFS 42,4% vs 39,6%, Fig.1). Analysing the FLT3-TKDmut subgroup 54 pts had normal karyotype, 4 other cytogenetic alterations (not high risk); 6 MDS-related gene mutations. 48% of pts received induction CT+Midostaurin, 52% CT alone. The CR rate was 79%, 11 pts (18%) were refractory or relapsed within 4 months and 2 (3%) dead early. Of 49 pts in CR1, 13 received SCT and 36 CT alone, 18 (29%) relapsed. Median follow up was 35 months. Age, performance status, comorbidities, coexisting genetic alterations and the use of Midostaurin in induction didn’t influence OS and EFS. While 2CT MRD clearance didn’t show a significant survival advantage (2CT MRD- vs MRD+: 3yOS 80,6 vs 61,8%, p=0,11 and 3yEFS 59,5 vs 42,8%, p=0,14), a deep reduction of EoC MRD impacted significantly on prognosis (EoC MRD- vs MRD+: 3yOS 85,7 vs 28% p<0,0001, 3yEFS 58,6 vs 10,6%, p<0,0001). Allogenic transplantation (SCT) in first CR, positively affected EFS (3yEFS 65,6 vs 38,8%, p=0,045), but not OS (3yOS 78,5% vs 63,2% p=0,19) and, according to MRD level, EoC MRD- showed no significant survival advantage of SCT (3yOS; 77,8 vs 84,2%; 3yEFS: 66,7 vs 51,4%). Given the retrospective nature of the study, prospective trials are needed to better understand the impact of SCT in CR1 according to MRD level. In our real-life cohort the prognosis was similar in all NPM1mut FLT3mut AML pts, regardless of the type of FLT3mut. A comparison to NPM1mut FLT3wt AML pts could better clarify the prognostic impact of FLT3-TKDmut.