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. 2025 Sep 1;131(17):e70055.
doi: 10.1002/cncr.70055.

Gilteritinib in FLT3-mutated acute myeloid leukemia: A real-world Italian experience

Roberto Cairoli  1   2 , Lorenzo Del Castello  3 , Silvia Imbergamo  4 , Elisabetta Pierdomenico  5 , Cristina Papayannidis  6 , Erika Borlenghi  7 , Calogero Vetro  8 , Patrizia Chiusolo  9 , Monica Fumagalli  10 , Clara Minotti  11 , Francesco Marchesi  12 , Massimo Bernardi  13 , Pellegrino Musto  14 , Nicola Fracchiolla  15 , Anna Candoni  16 , Monia Lunghi  17 , Maurizio Musso  18 , Fabio Guolo  19 , Donato Mannina  20 , Albana Lico  21 , Anna Maria Scattolin  22 , Monica Crugnola  23 , Sara Galimberti  24 , Gianpaolo Nadali  25 , Mauro Turrini  26 , Patrizia Zappasodi  27 , Elisabetta Todisco  28 , Claudia Basilico  29 , Giovanni Grillo  1 , Valentina Mancini  1 , Marta Riva  1 , Davide Paolo Bernasconi  3 , Rosa Greco  1
Affiliations

Gilteritinib in FLT3-mutated acute myeloid leukemia: A real-world Italian experience

Roberto Cairoli et al. Cancer. .

Abstract

Background and methods: This real-world study evaluated the clinical effectiveness of gilteritinib in 205 patients with relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) enrolled in the Italian expanded access since January 2018.

Results: Of the 205 patients, 124 (60.5%) received gilteritinib as a bridging therapy to allogeneic stem cell transplantation (allo-SCT), achieving complete remission in 52.4% (n = 65). The median overall survival (OS) for the entire cohort was 11.0 months, with estimated OS rates of 46.8% at 1 year and 28.5% at 3 years. Sixty patients (48% of those bridged) underwent allo-SCT after a median of 3.7 months on gilteritinib, achieving posttransplant OS rates of 65.2% at 1 year and 56.1% at 3 years. The acquisition of FLT3 mutations at relapse and the presence of TP53 co-mutations were significantly associated with inferior outcomes. Among 46 patients (22.4%) who relapsed after allo-SCT, gilteritinib treatment yielded an overall response rate (ORR) of 54.3%, a median OS of 11.1 months, and 1- and 3-year OS rates of 49.5% and 15.5%, respectively. Additionally, 35 patients (17.1%) previously treated with nonintensive chemotherapy received gilteritinib until disease progression or intolerance, achieving an ORR of 11.4%, a median OS of 5.9 months, and a 1-year OS rate of 29.0%.

Conclusions: These real-world data confirm that clinical outcomes achieved with gilteritinib in patients with R/R FLT3-mutated AML are consistent with those observed in pivotal clinical trials. Notably, approximately half of the transplant-eligible patients were successfully bridged to allo-SCT and demonstrated encouraging long-term survival.

Keywords: FLT3; acute myeloid leukemia; gilteritinib; real‐world; tyrosine kinase inhibitor.

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Conflict of interest statement

Roberto Cairoli reports consulting fees from AbbVie, Janssen Global Services, LLC, and Novartis; and fees for professional activities from Astellas Pharma, Jazz Pharmaceuticals, and Kite Pharma, Inc. Anna Candoni reports consulting fees from Amgen, Jazz Pharmaceuticals, Pfizer, and Servier Pharmaceuticals LLC; and fees for professional activities from AbbVie, Astellas Pharma, and Incyte. Nicola Fracchiolla reports fees for professional activities from AbbVie. Sara Galimberti reports grant and/or contract funding from AbbVie; and fees for travel from Jazz Pharmaceuticals and Novartis. Pellegrino Musto reports fees for professional activities from Novartis. Cristina Papayannidis reports fees for professional activities from AbbVie, Amgen, Astellas Pharma, Blueprint Medicine, Bristol‐Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals, Menarini International, Otsuka Pharmaceutical, Pfizer, Servier Pharmaceuticals LLC, and Syndax. Mauro Turrini reports honoraria from Johnson & Johnson, Astellas, and ItalFarmaco; fees for travel from Jazz Ph, AstraZeneca, and Johnson & Johnson; fees for professional activities from AstraZeneca and Astellas; and an unpaid role with the Regional Committee on Acute Leukemias. Calogero Vetro reports consulting fees from AbbVie and Jazz Pharmaceuticals. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Bar charts depicting the most frequent co‐mutated genes among patients who had FLT3 mutations at diagnosis (A) and those who acquired FLT3 mutations after diagnosis (B). FLT3‐ITD/TKD: Internal tandem duplication or tyrosine kinase domain mutations in the FLT3 gene. DNMT3A indicates DNA methyltransferase 3 α gene mutation; IDH1/2, isocitrate dehydrogenase 1 or 2 gene mutations; NPM1, nucleophosmin 1 gene mutation; TP53, tumor protein p53 gene mutation.
FIGURE 2
FIGURE 2
OS based on transplant eligibility and refractoriness to intensive chemotherapy. Kaplan–Meier curves showing OS in the full patient cohort (A) and stratified by transplant status: relapse posttransplant (B), transplant‐ineligible (C), and transplant‐eligible (D). (E and F) OS in patients refractory to intensive chemotherapy, with (F) further stratifying by number of prior chemotherapy lines (one line vs. two or more lines). OS indicates overall survival.
FIGURE 3
FIGURE 3
Outcomes following CR or CR with CRi. Crude cumulative incidences of hematopoietic stem cell transplant (blue line) and relapse or toxicity (orange line) in patients who achieved CR or CR with CRi. Events were analyzed using a competing risks framework from the time of best response. Shaded areas represent 95% CIs. Number at risk: patients remaining in follow‐up without either event at each time point. CI indicates confidence interval; CR, complete remission; CRi, incomplete hematologic recovery.
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