Fludarabine-Based Treatment vs Standard Regimen Among Patients With WT1-Mutated AML

Findings from a Retrospective Analysis 

Findings from a retrospective analysis published in Leukemia & Lymphoma indicated that a fludarabine-based regimen demonstrated improved relapse-free survival following allogeneic stem cell transplantation (alloSCT) compared to a traditional idarubicin/cytarabine (7 + 3) regimen for the treatment of patients with WT1-mutated acute myeloid leukemia (AML).  

This retrospective analysis examined the outcomes of alloSCT among 37 patients with WT1-mutated AML. Responses to treatment were assessed following 7 + 3 chemotherapy and conditioning regimens, including myeloablative or reduced-intensity fludarabine-based regimens. Additionally, an ex-vivo study assessed the sensitivity of WT1-mutated AML samples to various chemotherapy agents. 

Primary induction failure occurred in 40% of patients, with an early relapse rate of 18% after 7 + 3 chemotherapy. The study authors noted that all patients who experienced induction failure achieved complete remission following additional therapy. The outcomes between myeloablative and reduced-intensity fludarabine-based regimens were comparable. Notably, relapse-free survival was significantly improved among patients who received fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (G-CSF) (FLAG-IDA) prior to transplantation and/or a conditioning regimen containing fludarabine. 

The study revealed a heightened sensitivity of WT1-mutated AML samples to fludarabine and melphalan compared to non-WT1-mutated AML samples. There was no significant difference in sensitivity to cytarabine. 
Ahmed Aribi, MD, City of Hope National Medical Center, Duarte, California, and coauthors concluded, “Our data favor using a fludarabine-based induction for AML with WT1 mutation instead of 7 + 3. Fludarabine conditioning regimens for [allogeneic hematopoietic stem cell transplantation] (alloHCT) showed better [relapse-free survival] (RFS) but not [overall survival] (OS).”

Source: 

Aribi A, Salhotra A, Afkhami M, et al. WT1-mutated acute myeloid leukemia is sensitive to fludarabine-based chemotherapy and conditioning regimens. Leuk & Lymph. Published online August 3, 2023. doi: 10.1080/10428194.2023.2241096