60f0e26502cf400c34db07954e17e51d 306972.pdf 2b5314a6bf4cede159c097e6300deea159811808 306972.pdf 75badee6b04329286d70d79b3b0747e51bfa62c58b32a9649c0dc1d9b3477dd8 306972.pdf Title: Adjuvant Immunotherapy After Resected Melanoma: Survival Outcomes, Prognostic Factors and Patterns of Relapse Subject: Background: Anti-PD-1-based immunotherapy has improved outcomes in stage IIB to IV resected melanoma patients in clinical trials. However, little is known about real-world outcomes, prognostic factors and patterns of relapse. Methods: This is a retrospective multicenter observational study including patients with resected melanoma treated with subsequent anti-PD-1-based adjuvant immunotherapy. Data on clinical and demographic characteristics, delivered treatment, prognostic factors, time and pattern of relapse were collected. Results: We included 245 patients from eight centers; 4% of patients were at stage IIB-C, 80% at stage IIIA-D and 16% at stage IV. Recurrence-free survival (RFS) rates at 18 and 36 months were 60% and 48%, respectively, with a median RFS of 33.7 months. Prognostic factors associated with recurrence were melanoma primary site (HR 2.64, 95% CI 1.15–6.01) and starting adjuvant therapy more than 12 weeks after the last resection (HR 1.68, 95% CI 1.13–2.5); presence of serious immune-related adverse events was associated with better RFS (HR 0.4, 95% CI 0.19–0.87). Early relapses accounted for 63% of the total recurrences, with a higher number of metastatic sites (18%); in contrast, late relapses presented more frequently with brain metastases (20%). Conclusions: In our patients with resected melanoma who underwent anti-PD-1-based adjuvant immunotherapy, survival outcomes were worse than those reported in clinical trials. Primary melanoma site and time interval between the last resection and the start of adjuvant therapy were associated with survival. Keywords: melanoma; adjuvant immunotherapy; survival outcomes; prognostic factors; patterns of relapse Author: Sergio Martinez-Recio, Maria Alejandra Molina-Pérez, Eva Muñoz-Couselo, Alberto R. Sevillano-Tripero, Francisco Aya, Ana Arance, Mayra Orrillo, Juan Martin-Liberal, Luis Fernandez-Morales, Rocio Lesta, María Quindós-Varela, Maria Nieva, Joana Vidal, Daniel Martinez-Perez, Andrés Barba and Margarita Majem Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Sun Jan 5 08:04:40 2025 CET ModDate: Sun Jan 5 08:07:30 2025 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1472397 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XWOCXD+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 WDFCJN+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 AKGZVE+URWPalladioL-Bold Type 1 Custom yes yes yes 22 0 LRNWWD+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 EBSUHN+VnURWPalladioL Type 1 Custom yes yes yes 32 0 PDTLUH+CMSY10 Type 1 Builtin yes yes yes 64 0 KHFKBO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 78 0 KHFKBP+PalatinoLinotype CID TrueType Identity-H yes yes yes 81 0 KHFKCA+PalatinoLinotype TrueType WinAnsi yes yes no 87 0 KHFKCC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 90 0 KHFKIB+PalatinoLinotype TrueType MacRoman yes yes no 93 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 103 0 KHFNLG+TimesNewRoman TrueType WinAnsi yes yes no 117 0 KHFKBO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 120 0 KHFKBP+PalatinoLinotype CID TrueType Identity-H yes yes yes 123 0 KHFKCA+PalatinoLinotype TrueType WinAnsi yes yes no 129 0 KHFKCB+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 132 0 KHFKCC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 138 0 KHFKIB+PalatinoLinotype TrueType MacRoman yes yes no 141 0 KHFLDN+DengXian CID TrueType Identity-H yes yes yes 144 0 DPFBHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 167 0 DPFBIB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 170 0 DPFBID+PalatinoLinotype TrueType WinAnsi yes yes no 173 0 DPFBJF+Arial TrueType WinAnsi yes yes no 176 0 DPFBNF+SegoeUISymbol CID TrueType Identity-H yes yes yes 179 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-01-31 02:46:00 CET RepresentationInformation: 306972.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-01-30 19:26:46 CET Size: 1472397 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 290 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design Destination: subsection.2.1 Item: Title: Outcomes and Asessments Destination: subsection.2.2 Item: Title: Statistical Analysis Destination: subsection.2.3 Item: Title: Results Destination: section.3 Children: Item: Title: Patients and Treatment Characteristics Destination: subsection.3.1 Item: Title: Survival and Prognostic Factors Destination: subsection.3.2 Item: Title: Toxicities Destination: subsection.3.3 Item: Title: Patterns of Relapse Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Adjuvant Immunotherapy After Resected Melanoma: Survival Outcomes, Prognostic Factors and Patterns of Relapse Author: Sergio Martinez-Recio, Maria Alejandra Molina-Pérez, Eva Muñoz-Couselo, Alberto R. Sevillano-Tripero, Francisco Aya, Ana Arance, Mayra Orrillo, Juan Martin-Liberal, Luis Fernandez-Morales, Rocio Lesta, María Quindós-Varela, Maria Nieva, Joana Vidal, Daniel Martinez-Perez, Andrés Barba and Margarita Majem Subject: Background: Anti-PD-1-based immunotherapy has improved outcomes in stage IIB to IV resected melanoma patients in clinical trials. However, little is known about real-world outcomes, prognostic factors and patterns of relapse. Methods: This is a retrospective multicenter observational study including patients with resected melanoma treated with subsequent anti-PD-1-based adjuvant immunotherapy. Data on clinical and demographic characteristics, delivered treatment, prognostic factors, time and pattern of relapse were collected. Results: We included 245 patients from eight centers; 4% of patients were at stage IIB-C, 80% at stage IIIA-D and 16% at stage IV. Recurrence-free survival (RFS) rates at 18 and 36 months were 60% and 48%, respectively, with a median RFS of 33.7 months. Prognostic factors associated with recurrence were melanoma primary site (HR 2.64, 95% CI 1.15 6.01) and starting adjuvant therapy more than 12 weeks after the last resection (HR 1.68, 95% CI 1.13 2.5); presence of serious immune-related adverse events was associated with better RFS (HR 0.4, 95% CI 0.19 0.87). Early relapses accounted for 63% of the total recurrences, with a higher number of metastatic sites (18%); in contrast, late relapses presented more frequently with brain metastases (20%). Conclusions: In our patients with resected melanoma who underwent anti-PD-1-based adjuvant immunotherapy, survival outcomes were worse than those reported in clinical trials. Primary melanoma site and time interval between the last resection and the start of adjuvant therapy were associated with survival. 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