The Experience of Commercially Available CPX-351 Use As First-Line Treatment for Patients with Acute Myeloid Leukemia - a Report of Polish Adult Leukemia Group (PALG)

Introduction: Acute myeloid leukemia (AML) is a heterogeneous disease and one-fourth of cases are secondary to prior myelodysplastic or myeloproliferative neoplasms (sAML) or therapy related developing after former chemotherapy or radiotherapy (tAML). sAMLs and tAMLs are more frequent in older patients (pts) and their prognosis are often unfavorable due to adverse karyotype, high-risk molecular aberrations and resistance to standard chemotherapy (chtx). CPX-351 is a liposomal encapsulation of cytarabine and daunorubicin, with a molar ratio of 5:1. Phase II and III trials have shown an increased complete remission (CR) rate, progression free survival (PFS) and overall survival (OS) in patients with sAML and tAML receiving CPX-351, compared to standard 3 + 7 chtx. Most of real-world trials have shown an advantage of CPX-351 induction treatment, but the hematological and non-hematological toxicity of this schema is underlined. Aim: The aim of the study was to evaluate the real-world experience (RWE) with CPX-351 in Polish pts with sAML/tAML. Material and methods: PALG's center was searched for pts treated with commercially available CPX-351 from September 2022 to June 2024. A treatment outcome was assessed using U-Mann-Whitney, Chi-Square, Cox models and Kaplan-Meier estimate. Results: From 10 PALG's centers 45 sAML/tAML pts were identified, with 23 (51%) tAML. The median age was 60.4 years (range 51-65). Analysis of cytogenetic-molecular risk factors based on European Leukemia Net 2017 stratification revealed favorable, intermediate and poor risk groups in 7%, 42% and 51% AML pts, respectively. Response evaluation was available in 98% (n=44) of pts, after one or two induction cycles complete remission (CR)/CR with incomplete recovery (CRi) was 68% (n=30/44) and non-remission (NR) and early death was 24.7% (n=11/44), 2.3% (n=1/44), respectively. Negative minimal residual disease (MRD) after one or two induction cycle was documented in 42% pts with CR/CRi. Till June 2024, in patients who achieved CR/CRi, allogeneic hematopoietic cell transplantation (alloHCT) was performed in 33.3% (n=15) of pts, however, there are still pts who are awaiting for alloHCT. During the CPX-351 induction the median number of days with grade 4 neutropenia was 28 (range 19-37) and grade >3 thrombocytopenia was 31 (range 23-44). The median number of transfused packed red blood cell (PRBC) was 13 (range 10-16) and the number of platelet concentrate units was 36 (range 25-66). The median duration of antibiotic therapy was 22 days (range 14-31). Infectious complications were observed in 87% pts. Thirty eight percent of pts developed grade > 3 infections; including bacteriemia, neutropenic fever, pneumonia and colitis. The median time of follow up was 6.6 months (range 3.6-10.9). The median overall survival (OS) was not reached, with probability of 1-year survival 59% (95%CI: 38-81). The median disease-free survival (DFS) was 11.7 months (95%CI: 6.4-11.8) with the probability of 1-year DFS 21% (95%CI: 0-58). In the univariate Cox proportional hazard regression, a positive prognostic effect on the OS was observed only for CR/CRi achievement (HR=0.24, 95%CI: 0.06-0.95; p=0.041). The ELN 2017 risk groups, number of bone marrow blasts, white blood cell count, lactate dehydrogenase concentration, alloHCT did not affect the OS. In the multivariate Cox proportional hazard model none of the variables had a significant impact on the OS. Conclusions: Based on the results of our trial we may conclude that CPX-351 induction is a highly effective regimen in sAML/tAML with high CR/CRi rate as well as high number of CR/CRi with negative MRD and low early death rate. The tolerability and toxicity of the treatment is acceptable. The further continuing of this trial to collect higher number of pts and longer follow up is designed. AP and OR equivalently contributed to the study.