Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia : A Real-World Study by the CETLAM and PETHEMA Groups
Vives Polo, Susana (Universitat Autònoma de Barcelona. Departament de Medicina)
Quintela, David (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Morgades, Mireia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Cano-Ferri, Isabel (Hospital Universitari i Politècnic La Fe (València))
Serrano, Alfons (Hospital Universitari i Politècnic La Fe (València))
Acuña-Cruz, Evelyn (Hospital Universitari i Politècnic La Fe (València))
Cervera, Marta (Hospital Universitari Joan XXIII de Tarragona)
Díaz-Beyá, Marina (Hospital Clínic i Provincial de Barcelona)
Vidriales, María Belén (Hospital Universitario de Salamanca)
Raposo Puglia, José Ángel
Arnan, Montserrat (Hospital Universitario Puerta del Mar (Cadis, Andalusia))
Garrido Diaz, Ana (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Balerdi, Amaia (Hospital Universitario de Cruces (Barakaldo, País Basc))
Cabello, Ana Isabel (Hospital Universitario Nuestra Señora de Candelaria (Santa Cruz de Tenerife))
Herrera-Puente, Pilar (Hospital Universitario Ramón y Cajal (Madrid))
Serrano, Josefina (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Coll, Rosa (Hospital Universitari de Girona Doctor Josep Trueta)
Tormo, Mar (Hospital Clínic Universitari (València))
López-Marín, Javier (Hospital General Universitario de Alicante (Alacant, País Valencià))
Garcia-Avila, Sara (Hospital del Mar (Barcelona, Catalunya))
Casado, María Soledad (Complejo Hospitalario Universitario de Badajoz)
Padilla, Irene (Hospital Universitario de León)
Rodríguez-Macías, Gabriela (Hospital General Universitario Gregorio Marañón)
Calbacho, Maria (Hospital Universitario 12 de Octubre (Madrid))
Puchol, Ana (Hospital Universitario de la Princesa (Madrid))
Hernández, Agustín (Hospital Quirón Salud Málaga)
Torres, Melissa (Hospital Universitario de Gran Canaria Dr. Negrín)
Costilla-Barriga, Lissette (Hospital General San Jorge (Osca))
Colorado, Maria Mercedes (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Martínez-Cuadrón, David (Hospital Universitari i Politècnic La Fe (València))
Esteve Reyner, Jordi (Hospital Clínic i Provincial de Barcelona)
Montesinos, Pau (Hospital Universitari i Politècnic La Fe (València))

Data:	2024
Resum:	Relapsed/refractory FLT3-mutated acute myeloid leukemia (AML) is associated with a poor prognosis. Mutations in the FLT3 gene provide a target for therapeutic intervention. Two FLT3 inhibitors, gilteritinib and quizartinib, when used as single agents, have demonstrated efficacy in this context. The aim of our retrospective study was to compare the outcomes of 50 patients diagnosed with FLT3 -mutated AML treated with gilteritinib or quizartinib monotherapy, with results from phase 3 clinical trials and with other real-world studies. Despite differences among the cohorts, our findings confirm that gilteritinib and quizartinib monotherapy represent effective and tolerable treatment options for patients with relapsed/refractory FLT3 -mutated AML in real-world settings, with response and toxicity rates consistent with those reported in prior studies. Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3 mut) have a dismal prognosis. FLT3 mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3 mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. Results: The median age was 62. 5 years, and 52% were women. Most patients presented with FLT3 -ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4. 74 months and 2. 99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10. 77 months vs. 4. 24 months, p = 0. 016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3 mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	FLT3 mutations ; Acute myeloid leukemia ; Gilteritinib ; Quizartinib ; Real world data
Publicat a:	Cancers, Vol. 16 (November 2024) , ISSN 2072-6694

DOI: 10.3390/cancers16234028
PMID: 39682214

13 p, 824.7 KB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
Articles > Articles de recerca
Articles > Articles publicats