Comparable effectiveness of CPX-351 and HMA plus venetoclax in older AML patients

CPX-351 therapy did not result in different overall survival (OS) outcomes or response rates than venetoclax plus HMA therapy in patients with acute myeloid leukaemia (AML) between 60 and 75 years of age.

Both CPX-351 and venetoclax plus a hypomethylating agent (HMA) combination therapy have demonstrated to improve OS in older patients with AML2,3. Dr Justin Grenet (New York-Presbyterian/Weill Cornell Medical Center, NY, USA) and colleagues conducted a real-world, multicentre, retrospective chart review to compare the effectiveness of CPX-351 (n=211) versus venetoclax plus HMA (n=226).

Primary outcomes were response rate, OS, and relapse-free survival. Dr Grenet explained that CPX-351 therapy is usually prescribed to younger patients who are deemed fit enough to withstand intensive chemotherapy, whereas venetoclax plus HMA is mostly prescribed in older, frailer patients.

No significant difference regarding Overall Survival

The research team was mostly interested to compare treatment results in patients between 60 and 75 years of age, the age category that shows the highest treatment overlap.

In patients between 60 and 75 years of age, there was no significant difference regarding OS between the 2 treatment regimens (logrank-P=0.3375), despite the higher rates of haematopoietic stem cell transplantations (HSCT) in the CPX-351 arm (47.7%) compared with the venetoclax plus HMA arm (19.0%; P<0.001). Moreover, response rates did not favour one treatment over the other in this age category (59.2% vs 54.0%, respectively; P=0.41).

Further analyses on comorbidities and pre/post induction scores to follow

Subgroup analyses displayed an advantage of CPX-351 therapy in patients between 60 and 75 years who were TP53-positive (HR 0.66; P=0.013). Strata differentiating for prior myeloid malignancy, prior HMA use, or European LeukemiaNet (ELN) risk classification did not show superiority of one treatment regimen over the other.

Dr Grenet argued that the treatment regimens display comparable effectiveness in patients with AML between 60 and 75 years. Currently, the team is investigating comorbidities and pre- and post-induction fitness scores in the study population to further analyse which treatment regimen provides the most benefits for each subgroup of patients.

1. Grenet J, et al. Comparing Outcomes between Liposomal Daunorubicin/Cytarabine (CPX-351) and HMA + Venetoclax As Frontline Therapy in Acute Myeloid Leukemia. O615, ASH 2021 Scientific Sessions, 11–14 December.
2. Lancet JE, et al. J Clin Oncol. 2018;36(26):2684-2692
3. DiNardo CD, et al. NEJM. 2020;383:617-629