d7a48ec250a35fd6b586fe6dae1b1df8 pmc_11639769.pdf b26dd4921f05dd77cd62ad775fa224f45beba6f2 pmc_11639769.pdf d90c21b4ca3011258b9e56e49389945e5bb45710d3e37a1f04aeecc910bab025 pmc_11639769.pdf Title: Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups Subject: Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut 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 FLT3mut 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 FLT3mut 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. Keywords: FLT3 mutations; acute myeloid leukemia; gilteritinib; quizartinib; real world data Author: Susana Vives, David Quintela, Mireia Morgades, Isabel Cano-Ferri, Alfons Serrano, Evelyn Acuña-Cruz, Marta Cervera, Marina Díaz-Beyá, Belén Vidriales, José Ángel Raposo-Puglia, Montserrat Arnan, Ana Garrido, Amaia Balerdi, Ana Isabel Cabello, Pilar Herrera-Puente, Josefina Serrano, Rosa Coll, Mar Tormo, Javier López-Marín, Sara García-Ávila, María Soledad Casado, Irene Padilla, Gabriela Rodríguez-Macías, María Calbacho, Ana Puchol, Agustín Hernández, Melissa Torres, Lissette Costilla, Maria Mercedes Colorado, David Martínez-Cuadrón, Jordi Esteve and Pau Montesinos Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon Dec 2 10:12:49 2024 CET ModDate: Mon Dec 2 10:22:32 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 844497 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FFAYKL+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 XATOQH+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 BUOHNZ+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 YDZYNB+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 HKBJPQ+VnURWPalladioL Type 1 Custom yes yes yes 32 0 NWYVYM+CMSY10 Type 1 Builtin yes yes yes 65 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes yes 73 0 PANMLB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 95 0 PANMLD+PalatinoLinotype TrueType WinAnsi yes yes no 98 0 PANMLF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 101 0 PANMLB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 117 0 PANMLD+PalatinoLinotype TrueType WinAnsi yes yes no 120 0 PANMLF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 123 0 PANMLB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 144 0 PANMLD+PalatinoLinotype TrueType WinAnsi yes yes no 147 0 PANMLF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 150 0 PANOHB+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 165 0 PANMLB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 168 0 PANMLC+PalatinoLinotype CID TrueType Identity-H yes yes yes 171 0 PANMLD+PalatinoLinotype TrueType WinAnsi yes yes no 177 0 PANMLF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 180 0 PANNHD+PalatinoLinotype TrueType MacRoman yes yes no 183 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-06 02:45:09 CET RepresentationInformation: pmc_11639769.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-01-17 02:40:03 CET Size: 844497 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 329 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Methods Destination: section.2 Item: Title: Results Destination: section.3 Children: Item: Title: Patients and Treatment Destination: subsection.3.1 Item: Title: Outcomes Destination: subsection.3.2 Item: Title: Toxicity Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups Author: Susana Vives, David Quintela, Mireia Morgades, Isabel Cano-Ferri, Alfons Serrano, Evelyn Acuña-Cruz, Marta Cervera, Marina Díaz-Beyá, Belén Vidriales, José Ángel Raposo-Puglia, Montserrat Arnan, Ana Garrido, Amaia Balerdi, Ana Isabel Cabello, Pilar Herrera-Puente, Josefina Serrano, Rosa Coll, Mar Tormo, Javier López-Marín, Sara García-Ávila, María Soledad Casado, Irene Padilla, Gabriela Rodríguez-Macías, María Calbacho, Ana Puchol, Agustín Hernández, Melissa Torres, Lissette Costilla, Maria Mercedes Colorado, David Martínez-Cuadrón, Jordi Esteve and Pau Montesinos Subject: Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut 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 FLT3mut 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 FLT3mut 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. 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