5dd8ae59c1349d4b3b4aab540fa874a9 270617.pdf 7915729b0e9c80fba50e0b6ca106fa0291a34179 270617.pdf a0e056d3e31168e8d18d1060972fe6f0d343d2dc6559f49d7f4a171d99156e78 270617.pdf Title: Characteristics and Outcomes of Adult Patients in the PETHEMA Registry with Relapsed or Refractory FLT3-ITD Mutation-Positive Acute Myeloid Leukemia Subject: This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant. Keywords: acute myeloid leukemia; FLT3-ITD mutation; real-world outcomes; relapsed/refractory disease; salvage therapy Author: David Martínez-Cuadrón, Josefina Serrano, José Mariz, Cristina Gil, Mar Tormo, Pilar Martínez-Sánchez, Eduardo Rodríguez-Arbolí, Raimundo García-Boyero, Carlos Rodríguez-Medina, Carmen Martínez-Chamorro, Marta Polo, Juan Bergua, Eliana Aguiar, María L. Amigo, Pilar Herrera, Juan M. Alonso-Domínguez, Teresa Bernal, Ana Espadana, María J. Sayas, Lorenzo Algarra, María B. Vidriales, Graça Vasconcelos, Susana Vives, Manuel M. Pérez-Encinas, Aurelio López, Víctor Noriega, María García-Fortes, María C. Chillón, Juan I. Rodríguez-Gutiérrez, María J. Calasanz, Jorge Labrador, Juan A. López, Blanca Boluda, Rebeca Rodríguez-Veiga, Joaquín Martínez-López, Eva Barragán, Miguel A. Sanz, Pau Montesinos and on behalf of the PETHEMA Group Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jun 7 04:58:03 2022 CEST ModDate: Tue Jun 7 05:11:40 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1080013 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 10 0 PMLXUC+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 MJWJPY+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 IMCRDS+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 HCEJUO+URWPalladioL-BoldItal Type 1 Custom yes yes no 28 0 JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 51 0 VBAQIR+CMSY10 Type 1 Builtin yes yes no 73 0 JLZORU+EURM10 Type 1 Builtin yes yes no 83 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-25 02:26:08 CEST RepresentationInformation: 270617.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-05-24 10:50:06 CEST Size: 1080013 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 284 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Main Inclusion Criteria Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Data Extraction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Treatment Schedules Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Endpoints and Outcome Measures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: First-Line Therapy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Salvage Therapy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Stem Cell Transplantation in Second-Line Therapy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Survival Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: Title: Characteristics and Outcomes of Adult Patients in the PETHEMA Registry with Relapsed or Refractory FLT3-ITD Mutation-Positive Acute Myeloid Leukemia Author: David Martínez-Cuadrón, Josefina Serrano, José Mariz, Cristina Gil, Mar Tormo, Pilar Martínez-Sánchez, Eduardo Rodríguez-Arbolí, Raimundo García-Boyero, Carlos Rodríguez-Medina, Carmen Martínez-Chamorro, Marta Polo, Juan Bergua, Eliana Aguiar, María L. Amigo, Pilar Herrera, Juan M. Alonso-Domínguez, Teresa Bernal, Ana Espadana, María J. Sayas, Lorenzo Algarra, María B. Vidriales, Graça Vasconcelos, Susana Vives, Manuel M. Pérez-Encinas, Aurelio López, Víctor Noriega, María García-Fortes, María C. Chillón, Juan I. Rodríguez-Gutiérrez, María J. Calasanz, Jorge Labrador, Juan A. López, Blanca Boluda, Rebeca Rodríguez-Veiga, Joaquín Martínez-López, Eva Barragán, Miguel A. Sanz, Pau Montesinos and on behalf of the PETHEMA Group Subject: This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant. 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