New Combination Regimens vs. Fludarabine, Cytarabine, and Idarubicin in the Treatment of Intermediate- or Low-Risk Nucleophosmin-1-Mutated Acute Myeloid Leukemia: A Retrospective Analysis from 7 Italian Centers.

: Nucleophosmin-1 () mutation accounts for 30% of acute myeloid leukemia (AML) cases and defines either low- or intermediate-risk AML, depending on -ITD mutation. New combination regimens (NCRs), adding midostaurin and gemtuzumab ozogamicin (GO) to the 3 + 7 scheme, are commonly used, though there are no data that compare NCRs with intensive induction chemotherapy. : To evaluate the efficacy and safety of NCRs and FLAI in + AML, we retrospectively analyzed 125 patients treated with FLAI ( = 53) or NCRs ( = 72) at seven Italian Centers. : The median age was 61 years and 51/125 (41%) were -ITD+. The complete remission (CR) rate was 77%, slightly better with NCRs (83% vs. 68%; = 0.054). NCRs yielded a superior median overall survival (OS) (not reached (NR) vs. 27.3 months; = 0.002), though the median event-free survival (EFS) was similar (NR vs. 20.5 months; = 0.07). In low-risk AML, CR was higher in NCRs (94% vs. 72%, = 0.02), as were median OS (NR vs. 41.6 months; = 0.0002) and EFS (NR vs. 17.8 months; = 0.0085). In intermediate-risk AML (-ITD+), there were no differences in CR (60% vs. 71%; = 0.5), OS ( = 0.27), or EFS ( = 0.86); only allogeneic transplantation improved OS (NR vs. 13.4 months; = 0.005), regardless of induction regimen. The safety profile was similar, except for delayed platelet recovery with FLAI (22 vs. 18 days; = 0.0024) and higher-grade II-IV gastrointestinal toxicity with NCRs (43% vs. 18.8%; = 0.0066). Our data suggest the superiority of NCRs over FLAI in low-risk patients, while all outcomes were comparable in intermediate-risk patients, a setting in which only transplants positively impacted on survival.