PMID- 38318726
OWN - NLM
STAT- Publisher
LR  - 20240206
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Linking)
DP  - 2024 Feb 6
TI  - Effects of CTLA-4 Single Nucleotide Polymorphisms on Toxicity of 
      Ipilimumab-Containing Regimens in Patients With Advanced Stage Melanoma.
LID - 10.1097/CJI.0000000000000506 [doi]
AB  - Single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte-associated 
      protein 4 (CTLA-4) gene, an inhibitor of T-cell priming, are associated with auto 
      and alloimmunity. Studies implied a role for these SNPs as surrogate markers for 
      immunotherapy-outcome in patients with melanoma. However, no predictive SNPs are 
      defined to date. We analyzed different CTLA-4 SNPs in a large multicenter cohort 
      of patients with ipilimumab-treated melanoma and investigated possible 
      correlations with treatment-related outcomes. Archival blood and/or tumor tissue 
      samples were collected from 361 patients with advanced-stage ipilimumab-treated 
      (+/-nivolumab) in 6 Swiss and Dutch hospitals. Matrix-assisted laser 
      desorption/ionization-time of flight mass spectrometry based DNA genotyping was 
      performed for 10 different CTLA-4 SNPs: 49A>G, CT60G>A, Jo27T>C, Jo30G>A, 
      Jo31G>T, -658C>T, -1722T>C, -1661A>G, 318C>T, and C>T rs1863800. Associations 
      between different allele genotypes and occurrence of grade >/=3 adverse events 
      (AEs) and survival were tested using univariable logistic regressions or Cox 
      proportional hazard models. 262/361 (73%) patients could be analyzed; 65% of 
      those were males, the median age was 58 years, 39% showed a partial or complete 
      response, and 65% had >/=1 AEs. A TT-genotype of -1722T>C SNP was significantly 
      associated with a lower incidence of grade >/=3 AEs (P = 0.049), whereas the 
      GG-genotype of CT60G>A correlated with a higher incidence of grade >/=3 AEs (P = 
      0.026). The TT-genotype of Jo27T>C SNP (P = 0.056) and GG-genotype of Jo31G>T (P 
      = 0.046) were associated with overall survival. CTLA-4 SNPs might predict 
      treatment-related outcomes in patients with melanoma receiving ipilimumab. 
      Confirmatory studies are needed to fully exploit those findings as predictive 
      biomarkers for ipilimumab AEs.
CI  - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved.
FAU - de Joode, Karlijn
AU  - de Joode K
AD  - Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University 
      Medical Center, Rotterdam, the Netherlands.
FAU - Mora, Alfonso Rojas
AU  - Mora AR
AD  - Competence Center of Swiss Group for Clinical Cancer Research (SAKK), Bern, 
      Switzerland.
FAU - van Schaik, Ron H N
AU  - van Schaik RHN
AD  - Department of Clinical Chemistry, Erasmus MC University Medical Center, 
      Rotterdam, The Netherlands.
FAU - Zippelius, Alfred
AU  - Zippelius A
AD  - Department of Biomedicine, Division of Medical Oncology, University Hospital and 
      University of Basel, Basel, Switzerland.
FAU - van der Veldt, Astrid
AU  - van der Veldt A
AD  - Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University 
      Medical Center, Rotterdam, the Netherlands.
AD  - Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, 
      Rotterdam, the Netherlands.
FAU - Gerard, Camille Lea
AU  - Gerard CL
AD  - Precision Oncology Center, Lausanne University Hospital (CHUV), Lausanne, 
      Switzerland.
FAU - Laubli, Heinz
AU  - Laubli H
AD  - Department of Biomedicine, Division of Medical Oncology, University Hospital and 
      University of Basel, Basel, Switzerland.
FAU - Michielin, Olivier
AU  - Michielin O
AD  - Department of Medical Oncology, Lausanne University Hospital (CHUV), Lausanne, 
      Switzerland.
FAU - von Moos, Roger
AU  - von Moos R
AD  - Department of Oncology/Hematology, Cantonal Hospital Graubunden, Chur, 
      Switzerland.
FAU - Joerger, Markus
AU  - Joerger M
AD  - Department of Oncology/Hematology, Cantonal Hospital St. Gallen, St. Gallen, 
      Switzerland.
FAU - Levesque, Mitchell P
AU  - Levesque MP
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Aeppli, Stefanie
AU  - Aeppli S
AD  - Department of Oncology/Hematology, Cantonal Hospital St. Gallen, St. Gallen, 
      Switzerland.
FAU - Mangana, Johanna
AU  - Mangana J
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Mangas, Cristina
AU  - Mangas C
AD  - Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.
FAU - Trost, Nadine
AU  - Trost N
AD  - Department of Molecular Diagnostics and Research, Blood Transfusion Service 
      Zurich, Swiss Red Cross, Schlieren, Switzerland.
FAU - Meyer, Stefan
AU  - Meyer S
AD  - Department of Molecular Diagnostics and Research, Blood Transfusion Service 
      Zurich, Swiss Red Cross, Schlieren, Switzerland.
FAU - Parvex, Sandra Leoni
AU  - Parvex SL
AD  - Pathology Institute, Ente Ospedaliero Cantonale (EOC), Locarno, Switzerland.
FAU - Mathijssen, Ron
AU  - Mathijssen R
AD  - Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University 
      Medical Center, Rotterdam, the Netherlands.
FAU - Metaxas, Yannis
AU  - Metaxas Y
AD  - Department of Medical Oncology, Cantonal Hospital Muensterlingen, Muensterlingen, 
      Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20240206
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
SB  - IM
EDAT- 2024/02/06 06:43
MHDA- 2024/02/06 06:43
CRDT- 2024/02/06 05:31
PHST- 2023/08/30 00:00 [received]
PHST- 2023/10/16 00:00 [accepted]
PHST- 2024/02/06 06:43 [medline]
PHST- 2024/02/06 06:43 [pubmed]
PHST- 2024/02/06 05:31 [entrez]
AID - 00002371-990000000-00086 [pii]
AID - 10.1097/CJI.0000000000000506 [doi]
PST - aheadofprint
SO  - J Immunother. 2024 Feb 6. doi: 10.1097/CJI.0000000000000506.