Dose-Reduced FLA-IDA in Combination with Venetoclax Is an Effective and Safe Salvage Therapy in Relapsed and Refractory Acute Myeloid Leukemia (R/R AML)

Despite the development of targeted therapies in first-line AML, complete remissions (CR) cannot be achieved in 30-40%, and relapse rates remain high. In R/R AML the intensive treatment regimen of fludarabine, cytarabine, idarubicin combined with venetoclax (FLA-VIDA) showed improved remission rates compared to FLA-IDA. In this retrospective single-center analysis, we investigated the efficacy and safety of dose-reduced FLA-IDA with and without venetoclax to minimize the risk of infectious complications and excessive myelosuppression; Methods: Between 2011 and 2023, 89 R/R AML patients were treated with dose-reduced FLA-IDA (fludarabine 30 mg/m² day 1-4, cytarabine 2000 mg/m² day 1-4, idarubicin 10 mg/m² day 1 + 4). From 2019 onwards, venetoclax was added (day 1 100 mg, day 2 200 mg, day 3-14 400 mg); Results: Significantly improved response rates were observed with 60.0% vs. 38.8% CR/CRi (<i>p</i> = 0.0297) and 74.5% vs. 47.3% (<i>p</i> = 0.032) CR/CRi/MLFS for FLA-VIDA vs. FLA-IDA. Further, with FLA-VIDA significantly improved event-free survival (EFS) was observed (<i>p</i> = 0.026). Overall survival (OS) was similar in FLA-VIDA and FLA-IDA treated patients. The most common treatment-related toxicities were hematological adverse events, but they were comparable between groups. The time to neutrophil and platelet recovery were similar in responding patients treated with FLA-VIDA vs. FLA-IDA; Conclusions: Dose-reduced FLA-VIDA significantly improved response rates without increases in toxicity, showing promise for an improved R/R AML treatment.