Rechallenge With Switching Immune Checkpoint Inhibitors Following Autoimmune Myocarditis in a Patient With Lynch Syndrome
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Immune checkpoint inhibitors (ICIs) induce profound benefits in cancer patients with mismatch repair gene mutations or high levels of microsatellite instability. Herein, we present a case of a patient with history of Muir-Torre/Lynch syndrome and metastatic gastric adenocarcinoma in the presence of an MSH2 gene mutation. The patient was initially treated with a PD-1 inhibitor, pembrolizumab, but developed grade 4 myocarditis requiring treatment with infliximab and a prolonged steroid taper. Following discontinuation of pembrolizumab, surveillance testing showed no radiographic or endoscopic evidence of progression for 7 months, until biopsy results from a repeat upper endoscopy indicated local disease recurrence. The patient was subsequently rechallenged with another PD-1 inhibitor, nivolumab, at a 50% dose reduction without recurrent adverse events and eventually achieved a complete response after 13 cycles. This case highlights the relative importance of considering careful rechallenge with ICI therapy in patients with microsatellite instability–high malignancies and a high risk of severe adverse events.
Submitted January 14, 2023; final revision received March 28, 2023; accepted for publication April 11, 2023.
Disclosures: Dr. Bekaii-Saab has disclosed receiving institutional grant/research support from Agios Pharmaceuticals, Arya Pharma, Arcus, Atreca, Boston Biomedical, Bayer, Eisai, Celgene, Eli Lilly and Company, Ipsen, Clovis Oncology, Seattle Genetics, Genentech, Novartis, Mirati, Merus, AbGenomics, Incyte, Pfizer, and Bristol Myers Squibb; serving on a data safety monitoring board for FibroGen, Kintor Pharmaceutical Limited, AstraZeneca, Exelixis, Merck/Eisai, PanCan, and 1Globe Biomedical; serving on an advisory board for Imugene, Immuneering, Xilis, Replimune, Artiva, and Sun Biopharma; serving as an institutional consultant for Servier Pharma, Ipsen, Arcus Biosciences, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, Eisai, Merus, Merck KGaA, and Merck; serving as a consultant for Stemline Therapeutics Inc., AbbVie, Blueprint Medicines, Boehringer Ingelheim, Janssen Pharmaceuticals, Daiichi Sankyo, Natera, Treos Bio Limited, Celularity, Caladrius Biosciences, Exact Sciences, Sobi, BeiGene, Kanaph Therapeutics, AstraZeneca, Deciphera Pharmaceuticals, Zai Lab, Exelixis, Illumina, Foundation Medicine, Sanofi, and GSK; receiving royalties from UpToDate; and holding patents for WO/2018/183488 licensed to Imugene and WO/2019/055687 licensed to Recursion Pharmaceuticals. The remaining authors have disclosed not receiving any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.
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