Combinations of the BCL-2 inhibitor, venetoclax, with either hypomethylating agents (HMA), or low dose cytarabine (LDAC), have shown promising results in clinical trials of AML patients unfit for intensive therapy. We report on the efficacy and safety of AML patients that were treated with venetoclax combinations outside of clinical trials. Data on 133 patients with a mean age of 77 years is included. Complete remission (CR) + CR with incomplete count recovery (CRi) were achieved in 61% of patients. Relapse occurred in 25% of patients, with a median event free survival (EFS) of 11.7 months (95% CI, 10.09-13.35) among responding patients. At a median follow up of 8.7 months, the median overall survival (OS) was 9.8 months (95% CI 6.42-13.3) in the entire cohort. In multivariate analysis adverse karyotype was the only negative predictor of CR/CRi (p=0.03), while both ECOG performance status (PS) and adverse karyotype were significantly associated with shorter OS (p=0.023 and 0.038, respectively). Median OS was higher in patients achieving CR/CRi and in patients proceeding to allogeneic stem cell transplantation (allo-SCT). Treatment was well tolerated, with side effects similar to those described in the randomized clinical trials. Tumor lysis syndrome (TLS) occurred in 12% of patients. Our data support the efficacy and safety of venetoclax combinations in newly diagnosed AML patients not eligible for intensive therapy. According to our data, secondary AML patients could benefit from venetoclax combinations similarly to de-novo AML patients, and allo-SCT could be offered to selected patients achieving CR/CRi. This article is protected by copyright. All rights reserved.
Arie Apel, Yakir Moshe, Yishai Ofran, Alexander Gural, Ofir Wolach, Chezi Ganzel, Jonathan Canaani, Miri Zektser, Adrian Duek, Galia Stemer, Ilana Hellman, May Basood, Avraham Frisch, Chiya Leibovitch, Maya Koren-Michowitz