DP090 | CPX-351 LEADS TO HIGH RESPONSE RATES AND DURABLE OUTCOMES IN NPM1 MUTATED ACUTE MYELOID LEUKEMIA: AN ITALIAN MULTICENTRIC RETROSPECTIVE STUDY

Introduction: CPX-351 has been approved for treatment of Acute Myeloid Leukemia (AML) with Myelodysplastic Related Changes (AML-MRC) or therapy-related AML (t-AML) as per former WHO 2016 classification. Italian Real-World Experience confirmed benefit of CPX-351 in high-risk AML, and CPX-351 is now being explored as frontline treatment for de novo AML. However, data on the efficacy in NPM1 mutated AML remain limited, given rarity of this subgroup among t-AML, and results still immature from frontline trials. Aims: to analyze efficacy and outcome of CPX-351 in NPM1-mutated AML. Patients and results: 59 patients (median age 64 years, range 46-74, 52,5% aged≥65) (28/31, male/female) from 29 Italian Centers were retrospectively included in this study. Complete diagnostic testing were performed locally, and HSCT given as per local policy. Diagnosis of t-AML or AML-MRC were 19(32,2%) and 40(67,8%), respectively. Type A was most prevalent (88%) NPM1 mutation, while FLT3 was mutated in 12 patients (20%). Cytogenetics showed complex karyotype (>3 abnormalities) in 14 patients (23,7%). NGS data at diagnosis were available in 20 patients, with DNMT3a and IDH1/2 as prevalent mutations (19% respectively). Median number of comorbidities was 1 (Range 0-4). After induction 1, 47/59 patients (79%) achieved complete remission (CR); 2 achieved CR after induction 2, with a final CR rate of 83% (63% achieving MRD negativity). After inductions, 10 patients resulted refractory (16%). Complex karyotype was more frequent in refractory patients (p<0,005) with an OR of 3.12 (p=NS in a logistic stepwise regression analysis). Among responding patients, 8 (16,3%), 17 (34,8%) and 24 (48,9%) received none, one or two consolidation cycles, respectively. HSCT consolidation in first CR was performed in 17/49 responding patients (34,6%). Median RFS was of 19.6 months (CI 95% 14.8 - NA), and median of OS was of 20.2 months (CI 95% 17.21 – NA). In a Cox multivariate analysis RFS was significantly influenced by t-AML diagnosis (HR 48.5, p=0.026), FLT3 status (HR 32.1, p=0.035), number of consolidation (2 vs other)(HR 0,07, p=0.021) and HSCT in CR1 (HR 0.01, p=0.032), while OS was significantly influenced only by age (HR 1,34, p=0.012), with HSCT not significantly impacting on survival (Figure 1). Conclusions: In this large cohort of NPM1-mutated AML, CPX-351 was associated with good response and optimal survival outcome. Combinatory strategies with newer agents may further improve these results.