Managing post-transplant relapse in FLT3-mutated AML with gilteritinib
, 1, 1
Abstract
Acute myeloid leukemia (AML) represents 80 % of acute leukemias in the adult population. The mutation of the fms-like tyrosine kinase 3 (FLT3) receptor gene occurs in approximately 30% of patients with newly diagnosed AML, with FLT3-ITD mutation (ITD, internal tandem duplication) accounting for 25% of cases [1]. Approximately 50% of AML patients relapse and 10–40% are refractory to initial first-line treatment [2]. Currently, gilteritinib is the only registered FLT3 inhibitor for relapsed/refractory AML in Europe, which increases the rate of achieving complete responses and prolongs overall survival compared to salvage chemotherapy [3]. This clinical vignette highlights the challenges in the treatment of FLT3 AML patients.
Keywords: acute myeloid leukemiaFLT3-ITD mutationgilteritinibhematopoietic stem cell transplantation
References
- Daver N, Schlenk RF, Russell NH, et al. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019; 33(2): 299–312.
- Russell-Smith TA, Gurskyte L, Muresan B, et al. Efficacy of non-intensive therapies approved for relapsed/refractory acute myeloid leukemia: a systematic literature review. Future Oncol. 2022; 18(16): 2029–2039.
- Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or Chemotherapy for Relapsed or Refractory -Mutated AML. N Engl J Med. 2019; 381(18): 1728–1740.
- Wierzbowska A, Pluta A, Stelmach P, et al. A Phase 1 Dose-Escalation Study of the Cladribine Added to CPX-351 in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) - the Polish Adult Leukemia Group AML-1/2018 Study. Blood. 2023; 142(Supplement 1): 5914–5914.
- Andrews C, Pullarkat V, Recher C. CPX-351 in FLT3-mutated acute myeloid leukemia. Front Oncol. 2023; 13: 1271722.
- Perrone S, Ottone T, Zhdanovskaya N, et al. How acute myeloid leukemia (AML) escapes from FMS-related tyrosine kinase 3 (FLT3) inhibitors? Still an overrated complication? Cancer Drug Resist. 2023; 6(2): 223–238.
- Kennedy VE, Smith CC. FLT3 targeting in the modern era: from clonal selection to combination therapies. Int J Hematol. 2023 [Epub ahead of print].