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).
Martin Schönrock, Piet Sonnemann, Nina Michalowski, Michael Heuser, Felicitas Thol, Francis Ayuketang Ayuk, Christine Wolschke, Evgeny Klyuchnikov, Carsten Bokemeyer, Walter Fiedler, Sophia Cichutek
Author Information
Martin Schönrock: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Piet Sonnemann: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. ORCID
Nina Michalowski: Hospital Pharmacy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Michael Heuser: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany. ORCID
Felicitas Thol: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany. ORCID
Francis Ayuketang Ayuk: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Christine Wolschke: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Evgeny Klyuchnikov: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Carsten Bokemeyer: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Walter Fiedler: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. ORCID
Sophia Cichutek: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. ORCID
BACKGROUND: 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 AMLpatients were treated with dose-reduced FLA-IDA (fludarabine 30 mg/m day 1-4, cytarabine 2000 mg/m day 1-4, idarubicin 10 mg/m 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 ( = 0.0297) and 74.5% vs. 47.3% ( = 0.032) CR/CRi/MLFS for FLA-VIDA vs. FLA-IDA. Further, with FLA-VIDA significantly improved event-free survival (EFS) was observed ( = 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.
