AML-392 The Impact of MDS-Related Genetic Mutations on Clinical Outcomes in Patients With NPM1-Mutated Acute Myeloid Leukemia

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 24; p. S312
• Main Authors: Shahin, Omar, Makoseh, Mohammad, Abdelrahman, Zaid, AlRabie, Kamal, Khader, Renad, Alyamani, Ahmad, Dana, Waleed, Marie, Lina
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2024
• Subjects: AML; MDS-related genetic mutations; NPM1; STM; AML; NPM1; MDS-related genetic mutations; STM
• ISSN: 2152-2650
• DOI: 10.1016/S2152-2650(24)01197-2

Acute myeloid leukemia (AML) with NPM1 mutation carries a favorable prognosis. However, multiple clinical trials showed that the presence of co-mutations can affect this favorable outcome. Prognosis in patients with NPM1 and MDS-related genetic mutations (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2) is controversial. To assess clinical features and outcomes in patients with NPM1-mutated AML with MDS-related mutations, compared with those in NPM1-mutated AML patients without these specific genetic alterations. Medical records of adult AML patients (≥18 years) diagnosed and treated at King Hussein Cancer Center (KHCC) from 2017 through 2023 were reviewed. Complete response (CR), relapse-free survival (RFS), event-free survival (EFS), and overall survival (OS) were defined according to ELN 2022 guidelines. Patient characteristics were compared using Fisher's exact test and the Mann-Whitney test. Survival outcomes were evaluated by the Kaplan-Meier method. Among 250 adult patients diagnosed and treated for AML at KHCC, 49 (20%) had NPM1 mutations and were included in this analysis. The median age was 49 (range 24-78); 24 (49%) were males, 4 (8%) had secondary AML, and 44 (89%) exhibited normal cytogenetic analysis. FLT3/ITD was detected in 26 patients (53%), while MDS-related genetic mutations were found in 12 patients (24%). There was no statistically significant difference in baseline clinical characteristics between patients with MDS-related genetic mutations and those without. At the end of induction, 42 patients were evaluable for response, 36 of whom (85.7%) achieved CR. Twenty-two patients (45%) underwent alloSCT: 16 (72%) during CR1 and 6 (27%) due to relapsed or refractory disease. After a median follow-up of 32 months, there were no statistically significant differences in clinical outcomes between patients with MDS-related genetic mutations and those without in terms of RFS (not reached vs. 14.7 months, P=.86), EFS (8 months [95% CI, 4-11] vs. 15 months [95% CI, 9.4-20.6], P=.79), and OS (11 months [95% CI, 5.6-16.4] vs. 18 months [95% CI, 3.9-32.1], P=.82), respectively. In adult patients with NPM1-mutated AML, the presence of concurrent MDS-related genetic mutations doesn't appear to have an impact on clinical outcomes.