TY - JOUR AU - Swaminathan, Mahesh AU - Kantarjian, Hagop M AU - Levis, Mark AU - Guerra, Veronica AU - Borthakur, Gautam AU - Alvarado, Yesid AU - DiNardo, Courtney D AU - Kadia, Tapan AU - Garcia-Manero, Guillermo AU - Ohanian, Maro AU - Daver, Naval AU - Konopleva, Marina AU - Pemmaraju, Naveen AU - Ferrajoli, Alessandra AU - Andreeff, Michael AU - Jain, Nitin AU - Estrov, Zeev AU - Jabbour, Elias J AU - Wierda, William G AU - Pierce, Sherry AU - Pinsoy, Maria Rhona AU - Xiao, Lianchun AU - Ravandi, Farhad AU - Cortes, Jorge E PY - 2021/08/01 Y2 - 2024/03/28 TI - A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia and myelodysplastic syndrome JF - Haematologica JA - haematol VL - 106 IS - 8 SE - Articles DO - 10.3324/haematol.2020.263392 UR - https://haematologica.org/article/view/haematol.2020.263392 SP - 2121-2130 AB - FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in acute myeloid leukemia (AML) is associated with poor prognosis. We hypothesized that quizartinib, a selective and potent FLT3 inhibitor, with azacitidine (AZA) or low-dose cytarabine (LDAC) might improve the outcomes in patients with FLT3-ITD-mutated AML. In this open-label phase I/II trial, patients of any age receiving first-salvage treatment for FLT3-ITD AML or age >60 years with untreated myelodysplastic syndrome or AML were treated with quizartinib plus AZA or LDAC. Seventy-three patients were treated (34 frontline, 39 first-salvage). Among previously untreated patients, composite response (CRc) was achieved in 13/15 (87%, 8 CR, 4 Cri, 1 CRp) treated with quizartinib/AZA and 14/19 (74%, 1 CR, 8 CRi, 5 CRp) in quizartinib/LDAC. The median OS was 19.2 months for quizartinib/AZA and 8.5 months for quizartinib/LDAC cohort; RFS was 10.5 and 6.4 months, respectively. Among previously treated patients, 16 (64%) achieved CRc in quizartinib/AZA and 4 (29%) in quizartinib/LDAC. The median OS for patients treated with quizartinib/AZA and quizartinib/LDAC was 12.8 vs. 4 months, respectively. QTc prolongation grade 3 occurred in only 1 patient in each cohort. Quizartinib-based combinations, particularly with AZA, appear effective in both frontline and first-salvage for patients with FLT3-ITD-mutated AML and are well tolerated. ER -