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Relapsed or refractory (R/R) acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3) mutations remains a difficult and hard to treat entity. Gilteritinib is a potent oral FLT-3 inhibitor that improves overall survival in R/R AML, but studies are limited in combining gilteritinib with a hypomethylating agent and venetoclax treatment backbone (HMA-VEN-GILT). Here we report our experience with HMA-VEN-GILT for 22 R/R FLT3 AML patients. HMA-VEN-GILT yielded an ORR of 77.3% (17/22), CR 4.5% (1/22), CRi 13.6% (3/22), MLFS 59.1% (13/22). Median follow-up was 10.4 months with a relapse rate of 29.4% (5/17), median time to relapse of 69 days (range 35–298 days), 6-month overall survival of 84%, and median OS of 10.1 months. Additionally, 36.4% (8/22) of patients proceeded to hematopoietic stem cell transplant. In conclusion, HMA-VEN-GILT for the treatment of R/R FLT3 AML is feasible and can be used as a bridge to allogeneic transplantation. [ABSTRACT FROM AUTHOR]

We conducted a retrospective analysis of WT1-mutated acute myeloid leukemia (AML) patients who underwent allogeneic stem cell transplant. Thirty-seven patients with WT1-mutated AML were identified. Primary induction failure (40%) and early relapse rate (18%) after idarubicin/cytarabine (7 + 3) chemotherapy were observed. All patients with induction failure subsequently achieved CR with additional chemotherapy. There was no significant difference between outcomes after myeloablative vs. reduced intensity (Fludarabine/Melphalan [Flu/Mel]) conditioning regimens. RFS but not OS was significantly better in patients who received FLAG-IDA prior to transplant and/or a fludarabine-containing conditioning. In an independent ex vivo study, WT1-mutated AML samples exhibited greater sensitivity to fludarabine (p = 0.026) and melphalan (p = 0.0005) than non-WT1-mutated AML samples while there was no difference between sensitivity to cytarabine. Our data favor using a fludarabine-based induction for AML with WT1 mutation instead of 7 + 3. Fludarabine conditioning regimens for alloHCT showed better RFS but not OS. [ABSTRACT FROM AUTHOR]

Intensive treatment regimens for relapsed/refractory (R/R) acute myeloid leukemia (AML) generally include an anthracycline, cytarabine, with or without a purine analog. In patients who cannot tolerate an anthracycline due to comorbidities, one may consider using etoposide. Given the ongoing fludarabine shortage, it has prompted the switch to other purine analogs, such as cladribine, in combination with cytarabine and etoposide in patients who may be eligible for intensive chemotherapy but not able to tolerate an anthracycline due to comorbidities or cardiotoxicity risks. Here, we present 4 patients who received a cladribine, cytarabine, and etoposide (CCE) based regimen for R/R AML. There were no significant therapy-related adverse events, dose holds, or delays. Two out of 3 evaluable patients were successfully bridged to allogeneic transplant, and one is pending another cycle of chemotherapy as a bridge to transplant. The CCE regimen offers a potential option for patients with R/R AML in need of an anthracycline-free salvage regimen during a fludarabine shortage. [ABSTRACT FROM AUTHOR]