BCL-2 expression in AML patients over 65 years: Impact on outcomes across different therapeutic strategies

BCL-2 overexpression has been associated with resistance to chemotherapy and reduced survival in acute myeloid leukemia (AML), but few data are available in elderly patients, a subset accounting for majority of AML cases and with dismal prognosis. We retrospectively analyzed 113 AML patients aged ≥65 years treated with 3 + 7 chemotherapy (n = 51) or hypomethylating agents (HMAs) (n = 62), evaluating the role of BCL-2 expression on complete remission (CR) and overall survival (OS). BCL-2 was expressed in 81 patients (72%), more frequently in those with unfavorable cytogenetic-molecular risk. CR was achieved in 34.5% cases, without differences according to BCL-2 expression or induction therapy. In the whole population 1-year OS was 39%, similar in BCL-2+ and BCL-2-cases. In BCL-2 positive patients OS was superior with HMAs (56% vs. 25% with 3 + 7; p = 0.02), while no advantage for HMA was found in BCL-2 negative cases (36% vs. 27% for 3 + 7). Therapy with HMAs was the only factor associated with longer OS in BCL-2+ AML by multivariable analysis. Use of HMAs, possibly in combination with BCL-2 inhibitors, appears to be particularly appealing in BCL2+ AML, where it is associated with superior survival.