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

TL;DR

This study compares new drug combinations with traditional chemotherapy for a specific type of leukemia, finding better outcomes with new treatments in low-risk patients.

Contribution

The study provides the first retrospective comparison of new combination regimens with standard chemotherapy in NPM1-mutated AML.

Findings

New combination regimens showed better overall survival in low-risk NPM1+ AML patients.

There was no significant difference in outcomes between regimens for intermediate-risk patients.

Allogeneic transplantation improved survival in intermediate-risk patients regardless of treatment.

Abstract

Background: Nucleophosmin-1 (NPM1) mutation accounts for 30% of acute myeloid leukemia (AML) cases and defines either low- or intermediate-risk AML, depending on FLT3-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. Methods: To evaluate the efficacy and safety of NCRs and FLAI in NPM1+ AML, we retrospectively analyzed 125 patients treated with FLAI (n = 53) or NCRs (n = 72) at seven Italian Centers. Results: The median age was 61 years and 51/125 (41%) were FLT3-ITD+. The complete remission (CR) rate was 77%, slightly better with NCRs (83% vs. 68%; p = 0.054). NCRs yielded a superior median overall survival (OS) (not reached (NR) vs. 27.3 months; p = 0.002), though the median event-free survival (EFS) was similar (NR vs. 20.5 months; p = 0.07). In low-risk AML, CR was higher in NCRs (94% vs. 72%, p = 0.02), as were median OS (NR vs. 41.6 months; p = 0.0002) and EFS (NR vs. 17.8 months; p = 0.0085). In intermediate-risk AML (FLT3-ITD+), there were no differences in CR (60% vs. 71%; p = 0.5), OS (p = 0.27), or EFS (p = 0.86); only allogeneic transplantation improved OS (NR vs. 13.4 months; p = 0.005), regardless of induction regimen. The safety profile was similar, except for delayed platelet recovery with FLAI (22 vs. 18 days; p = 0.0024) and higher-grade II–IV gastrointestinal toxicity with NCRs (43% vs. 18.8%; p = 0.0066). Conclusions: 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.

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