P549: efficacy and toxicity of cpx-351 in patients with high-risk acute myeloid leukemia (aml): the multicenter real-world experience from the “italian triveneto registry”.

Background: CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, has been approved for the treatment of patients with newly diagnosed therapy-related Acute Myeloid Leukemia (t-AML) or AML with myelodisplasia-related changes (MRC-AML), improving survival probabilities in comparison with standard chemotherapy. Aims: To provide more clinical data we describe the Italian experience with CPX-351 as first-line therapy in a real world setting, outside of clinical trials or compassionate use program. Methods: We performed a preliminary analysis from cohort of 103 newly diagnosed AML patients (pts) treated in-label with CPX-351 in 11 Italian Hematological Centers (Udine, Treviso, Mestre, Padua, Verona, Bolzano, Aviano, Vicenza, Trento, Castelfranco Veneto, Trieste) from August 2019 to August 2022. Median age at diagnosis was 65 yrs (range 34-83). Sixty-two pts (60%) were diagnosed with secondary AML (sAML) evolving from myelodisplastic syndrome, 21 pts with MRC-AML (20%) and 20 patients with t-AML (19%). The cytogenetic risk (according to ELN 2017) was adverse in 48/103 pts (46.6%), intermediate in 46/103 (44.6%) and favorable in 7/103 (6.8%). In our cohort, 27 pts (26.2%) showed a complex kariotype. Median white blood cells count at diagnosis was 3,5x109/L. A total of 31 pts (30%) had been treated with hypomethylating agents (azacitidine) for anteceding MDS before initiation of CPX-351. All pts received the induction cycle at a standard dose of 44 mg/m on day 1, 3 and 5. 55/103 pts (53,3%) received at least 2 courses of CPX-351 and 46/103 pts (44.6%) proceeded to allogeneic hematopoietic stem cells transplant (HSCT). Results: In 97 evaluable pts the Overall Response Rate (ORR=CR+CRi) after the induction course was obtained in 76 pts (73.7%) with a median of 38 days from start of therapy. After a median follow up of 9.5 months (range 0.23-35.5) we observed a median response duration of 8 months (range 0.5-32). At last follow-up, 60/103 pts (58%) were still alive while the main cause of death was disease progression (in 30 out of 43 deceased pts, 69.7%). Twelve-months overall survival was 68.4%, while in the subset of patients that underwent HSCT the observed twelve-months OS was 91.5%. Multivariate analysis of factors affecting response showed no statistically significant predictors of a lower response. CPX-351 was generally well tolerated without onset of severe mucositis. The most common toxicities were myelosuppression and infective complications with 106 documented infections after induction. Three pts (2.9%) died within the first 30 days from induction during the aplasia phase due to an infection: 2 cases of pneumonias and 1 case of septic shock. Summary/Conclusion: These data confirm the efficacy and the emerging role of CPX-351 in the real word management of high risk AML, as well as the importance of HSCT consolidation in this particular subset of AML pts. Future directions include determining dose optimization with CPX-351 to induce an MRD-negative at transplant and studying new combination with target therapies. Keywords: Acute myeloid leukemia