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This document presents data on the outcomes and toxicities of a treatment regimen for older adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML). The study found that the treatment approach, which included induction chemotherapy with the addition of midostaurin, resulted in a high complete remission rate and a median overall survival of 9.3 months. Additionally, a significant number of patients underwent allogeneic hematopoietic stem cell transplantation (allo-HCT) with favorable outcomes. The authors conclude that this treatment approach is feasible and effective for older adults with FLT3-mutated AML. However, the study lacked long-term follow-up and data on minimal residual disease achievement and allo-HCT outcomes. [Extracted from the article]

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]

Patients living with HIV are now living longer due to increased access to antiretroviral therapy (ART) and a decrease in acquired immunodeficiency syndrome-defining cancer (ADC). However, increasing age and previous chemotherapy exposure for ADC (e.g., anthracyclines and topoisomerase inhibitors) are factors that may increase the risk of developing therapy-related myelodysplastic syndrome and acute myeloid leukemia (AML) and highlight an unmet need. There are no established guidelines for the treatment of AML in patients with HIV and the literature is limited to treatment outcomes and experience. In addition, cladribine, a purine analog used in AML, has a package insert warning to avoid administration with concurrent agents that undergo phosphorylation, which include HIV ART backbones (e.g., nucleoside reverse transcriptase inhibitors [NRTI]). Whether concurrent NRTI-based ART is deliverable with AML induction chemotherapy has not been reported previously. In our single-center experience of seven HIV-AML patients, all patients continued concurrent ART with induction chemotherapy. In 6 evaluable patients, three (50%) of patients went into complete remission (CR). Five (71.4%) patients were able to proceed to allogenic hematopoietic stem cell transplantation (HCT). Median OS was 16.6 months, with patients who received HCT having longer median OS compared to those who were unable to proceed to HCT (49.6 months vs. 3.4 months). Interestingly, none of the patients who received AML regimens that included fludarabine were able to obtain a response. On the contrary, 4 patients who received AML regimens that utilized cytarabine given over a prolonged period of time (e.g., 7 + 3, liposomal daunorubicin/cytarabine) achieved a CR rate of 75%. Concurrent HIV ART and AML induction chemotherapy is deliverable, although much remains to be investigated on potential drug interactions between purine analog-based chemotherapy and HIV ART. [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]

Rearrangements of I lysine [K] methyltransferase 2 A i ( I KMT2A i ) gene, previously known as the I MLL i gene, occur in 3 to 7% of adult patients with de novo AML and are enriched in therapy-related disease, particularly after treatment with topoisomerase II inhibitors [[1]]. Response and survival of patients with KMT2A rearranged acute myeloid leukemia (AML) receiving venetoclax in combination with hypomethylating agent therapy (HMA). The inferior prognosis of KMT2A rearranged AML patients undergoing alloSCT presents an opportunity for post-transplant maintenance trials with therapies targeting KMT2A. [Extracted from the article]

The 1-year OS for HCT patients (21 patients) was 85% (95% CI 61-95%) compared to 41% (95% CI 16-65%) in non-HCT patients in cCR (14 patients). The 1-year LFS in patients who underwent HCT (21 patients) was 67% (95% CI 41-84%) I versus i 33% (95% CI 10-57%) in non-HCT patients in cCR (14 patients). [Extracted from the article]

Midostaurin is a multikinase inhibitor approved for the treatment of adult patients with newly diagnosed FMS-like tyrosine kinase 3 mutated (FLT3m) acute myeloid leukemia (AML). Azole antifungal medications are commonly used in AML and are known to interact with anti-cancer drugs such as midostaurin through the CYP3A pathway. However, there are no midostaurin related dose modifications recommended with strong CYP3A inhibitors.We retrospectively reviewed 40 patients between 2017–2022 and compared efficacy and safety outcomes in patients who received azole antifungals concurrently to those who did not receive an azole or received it sequentially to midostaurin for treatment of FLT3m AML.Median age of both groups was approximately 55 years and 70% of patients harbored FLT-3 internal tandem duplication mutations. Most patients in the concurrent arm were on either posaconazole (33%) or isavuconazole (50%) for antifungal prophylaxis and micafungin (72%) for the sequential/no azole arm. Overall CR/CRi rate with concurrent versus sequential/no azole were 72% and 77%, and non-hematologic grade 3 toxicities were 22% and 40% (p = 0.21), respectively. Rates of dose reductions (6% vs. 0%, p = 0.26) and held doses (17% vs. 14%, p = 0.79) were not different between concurrent and sequential/no azole. There were no differences in the rates of new fungal infection during induction between the two groups.Azoles given concurrently or sequentially with midostaurin were found to be equally safe and effective in the treatment of newly diagnosed FLT3 AML. Additional confirmatory studies are needed due to our limited sample size. [ABSTRACT FROM AUTHOR]