Purpose: The prognosis of patients with unfit or relapsed/refractory (R/R) AML remains poor. Venetoclax (VEN) has been shown to exhibit anti-leukemia stem cell activity; however, few studies have been published on the efficacy and safety of VEN combined with both hypomethylating agents (HMAs) and low-dose chemotherapy for patients with unfit or R/R AML.
Methods: This study retrospectively analyzed the clinical characteristics, treatment details, safety profile and clinical outcomes of patients with unfit or R/R AML treated with VEN+ HMAs+ half-dose CAG (LDAC, aclarubicin and granulocyte colony-stimulating factor).
Results: A total of 24 AML patients were involved in the study, of whom 13 (54.2%) were in the unfit group, and 11 (45.8%) were in the R/R group. FLT3 and IDH (8/24, 33.3%) were the most common gene aberrations. Patients in the R/R group were found to be more likely to carry KIT (5/11, 45.5%) compared with the unfit group (0/13, 0%) (P = 0.006). The ORR observed during the study was 83.3% (20/24; 14 CR, 2CRi, 4PR). In the unfit group, 11/13 (84.6%) patients achieved cCR (10 CR and 1 CRi); while 5/11 (45.5%) R/R patients achieved response (4 CR and 1 CRi). CR was observed in all AML patients with TP53 (5/5), GATA2 (3/3), CEBPA (3/3) and ASXL1 (3/3). The most common adverse events (AEs) during VEN+ HMAs+ half-dose CAG therapy were persistent cytopenias and infections.
Conclusion: The results of this study confirm that VEN+ HMAs+ half-dose CAG is associated with promising efficacy (even high-risk molecular patterns) and tolerable safety profile in patients with unfit or R/R AML. Yet, the study involves only a small sample size, which should not be overlooked. As such, further studies on the efficacy of VEN combined with HMAs and half-dose CAG regimen in AML patients are essential.
Keywords: acute myeloid leukemia, BCL2 inhibitor, venetoclax, combined chemotherapy