Effectiveness of Gilteritinib Beyond Second‐Line Therapy in Relapsed/Refractory FLT3 ‐Mutated Acute Myeloid Leukemia: A Real‐World Multicenter Study of 171 Patients
Year: 2025
Type: article
Study design: Observational Study
Abstract: Gilteritinib is a selective FLT3 inhibitor approved for the treatment of relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) following ≥ 1 prior line of therapy. However, data on its effectiveness in later-line settings is limited. We conducted a multicenter, retrospective study including 171 adult patients with R/R FLT3-mutated AML who received gilteritinib as third-line or beyond between August 2017 and March 2024 across centers in Italy, Spain, the United Kingdom, and Turkey. The primary endpoint was overall survival (OS). Secondary endpoints included overall response rate (ORR), composite complete remission (cCR), duration of response. Among the 171 patients, 84% carried FLT3-ITD mutations and 26% had received ≥ 3 prior lines of therapy. The cCR rate was 28%, and ORR was 47%. Patients who were younger and presented with relapsed (vs. refractory) disease had better outcomes. Prior exposure to venetoclax or allogeneic hematopoietic stem cell transplantation (HSCT) was associated with inferior response. Gilteritinib enabled HSCT in 12% of patients. Median OS was 7.1 months (95% CI, 5.9-10.1), and in Cox-regression analysis was significantly improved among responders and those who underwent HSCT (median OS: 21.5 months; 95% CI, 12.8-NR). Prior venetoclax exposure was associated with shorter survival (5.7 months; 95% CI, 5.1-8.8). On multivariate analysis, previous exposure to venetoclax and FLT3 inhibitors was the strongest predictor of reduced response rates. Despite heavy pretreatment, gilteritinib retained clinically relevant activity in later-line R/R FLT3-mutated AML. Its use beyond second-line may serve as a bridge to HSCT in selected patients. Resistance mechanisms, particularly following venetoclax, remain a therapeutic challenge. These data support the continued use of gilteritinib beyond second-line and highlight the need for prospective studies to optimize sequencing strategies.
Source: American Journal of Hematology
DOI: 10.1002/ajh.70142
Authors: Matteo Molica, Gema Miralles, Richard Dillon, Mario Annunziata, Faisal Basheer, Juan M. Bergua, Ferran Vall‐Llovera Calmet, Victoria Campbell, Denis Cetin, Gaetano Cimino, Giulia Ciotti, Andrea Corbingi, Laura De Fazio, Hasim Atakan Erol, Vincenzo Federico, Cristina Gil, Yasa Gul Mutlu, Amaia Balerdi Malcorra, Sabrina Mariani, Carla Mazzone, Antonino Mulè, Gerardo Musuraca, Anjum Khan, Mariana Norata, Jenny O'Nions, Fanny Erika Palumbo, Cristina Papayannidis, Anna Lina Piccioni, Maria Teresa Olave Rubio, Jackeline Sanchez‐Tovar, Istemi Serin, Alessandra Serrao, Omur Gokmen Sevindik, Giuseppe Sucato, Marina Aurora Urbano, Calogero Vetro, Susana Vives, Marco Rossi, Maria Paola Martelli, Pau Montesinos, Jad Othman, Salvatore Perrone
Institutions: Azienda Ospedaliero-Universitaria "Renato Dulbecco", Hospital General Universitario de Elche, King's College London, Ospedale Antonio Cardarelli, Addenbrooke's Hospital, Hospital San Pedro de Alcántara, University Hospital Mútua de Terrassa, Mútua Terrassa, Western General Hospital, Ege University, University of Perugia, Azienda Ospedaliera di Perugia, Istituto Oncologico Veneto, Ospedale Santa Maria Goretti, Kocaeli Üniversitesi, Ospedale Vito Fazzi, Hospital General Universitario de Alicante Doctor Balmis, Gaziantep Şehir Hastanesi, Hospital de Cruces, Azienda Ospedaliera Sant'Andrea, Sapienza University of Rome, St. Eugenio Hospital, Ospedale Vincenzo Cervello, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Leeds Teaching Hospitals NHS Trust, University College Hospital, University College London Hospitals NHS Foundation Trust, University College London, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco", Istituto di Ematologia di Bologna, Azienda Ospedaliera San Giovanni Addolorata, Hospital Clínico Universitario Lozano Blesa, Hospital Rio Carrion, İstanbul Başakşehir Çam ve Sakura Şehir Hastanesi, Azienda Ospedaliera San Camillo-Forlanini, Istanbul Florence Nightingale Hospital, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" di Palermo, Ospedale A. Perrino, Ospedale di Bolzano, Azienda Sanitaria dell'Alto Adige, Hospital Universitari Germans Trias i Pujol, Hospital Universitari i Politècnic La Fe
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,450
Award: G7939660589
OpenAlex ID: W4416536681