Single-center retrospective clinical evaluation of venetoclax combined with HMAs and half-dose CAG in the treatment of unfit or refractory/relapsed AML

Abstract:

Purpose The prognosis of unfit or relapsed/refractory (R/R) AML patients remains poor. Venetoclax has been proved to have anti-leukemia stem cell activity. However, there is little published information on the efficacy and safety of VEN combined with both demethylated drugs and half-dose chemotherapy in the treatment of unfit or R/R AML patients.

Methods In this study, we retrospectively analyzed the clinical characteristics, treatment details, safety profile and clinical outcomes of unfit or R/R AML patients who were treated with VEN+ HMAs+ half-dose CAG.

Results A total of 21 AML patients were involved in the study, 11 patients (52.4%) were in the unfit group, while 10 patients (47.6%) were in R/R group. FLT3 (6/21, 28.6%) was the most common gene aberration. Patients in the R/R group were found more likely to carry KIT (5/ 10, 50%) when compared to the unfit group (0/11, 0%) (P = 0.012). The median duration of CR+ CRi was 11.5 months (95% CI 8.9 to 14.1). Twelve patients achieved CR (57.1%), two CRi (9.5%), and three PR (14.3%), for an ORR 80.9% (17/21) and cCR 66.7% (14/21). CR was observed in 100% (5/5) AML patients with TP53, 80% (4/5) AML patients with IDH, 75% (3/4) AML patients with NPM1, 50% (3/6) AML patients with FLT3, 40% (2/5) AML patients with KIT, 40% (2/5) AML patients with DNMT3A, and 20% (1/5) AML patients with RUNX1. The most common AEs during VEN+ HMAs+ half-dose CAG therapy were persistent cytopenia, infection and gastrointestinal symptoms (decreased appetite, nausea, vomiting and diarrhea).

Conclusion The results of this investigation show that VEN+ HMAs+ half-dose CAG demonstrated promising efficacy (even high-risk cytogenetics) and a tolerable safety profile in unfit or R/R AML patients.