{"doi":"10.3389/fonc.2022.836845","title":"Case Report: Delayed Onset Multi-Organ Toxicities in a Melanoma Patient Achieving Complete Response to BRAF/MEK Inhibition","abstract":"Autoimmune toxicities, while common following treatment with cancer immunotherapies, are not well-characterized in patients treated with BRAF/MEK inhibitors. Emerging data suggest that autoimmune effects may be linked with superior responses to both treatment modalities; however, there is little evidence describing mechanisms of immune-related toxicity for patients on BRAF/MEK inhibitors. Here we describe the experience of a 59-year-old HLA-A2, A29, B27-positive male with recurrent/metastatic melanoma. After progression on checkpoint inhibitor therapy, he was treated with dabrafenib/trametinib followed by encorafenib/binimetinib, which were well-tolerated and resulted in a complete response. Eighteen months into BRAF/MEK inhibitor therapy, and three months after initially finding a complete response, he developed a series of sudden-onset, severe toxicities: namely, bilateral panuveitis, cytopenias, joint pain, skin rash, hypercalcemia, and interstitial nephritis, which led to BRAF/MEKi cessation. Immunological analyses revealed induction of a peripheral type-17 cytokine signature characterized by high IL-23, IL-6, IL-10, IL-17A/F, IL-1β, and IL-21 among other cytokines in plasma corresponding with the height of symptoms. These findings highlight a novel instance of delayed autoimmune-like reaction to BRAF/MEK inhibition and identify a possible role for Th/Tc17 activation in their pathogenesis thus warranting future clinical and immunological characterization.","journal":"Frontiers in Oncology","year":2022,"id":267532,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9392,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":354296,"name":"Michael B. Ware","orcid":"0000-0002-6139-1952","position":1,"is_corresponding":false},{"id":775982,"name":"Aditya Rali","orcid":"0000-0001-8594-4593","position":2,"is_corresponding":false},{"id":226153,"name":"Susanne L. Linderman","orcid":"0000-0003-3297-3774","position":3,"is_corresponding":false},{"id":360927,"name":"Jessica G. Shantha","orcid":"0000-0002-4449-8598","position":4,"is_corresponding":false},{"id":251259,"name":"David H. Lawson","orcid":"0000-0002-9474-8321","position":5,"is_corresponding":false},{"id":928588,"name":"Melinda Yushak","orcid":"0000-0001-7076-3706","position":6,"is_corresponding":false},{"id":603196,"name":"Robert A. Swerlick","orcid":"0000-0002-9802-4144","position":7,"is_corresponding":false},{"id":314041,"name":"Chrystal M. Paulos","orcid":"0000-0002-0784-2601","position":8,"is_corresponding":false},{"id":250800,"name":"Steven Yeh","orcid":"0000-0002-5417-7771","position":9,"is_corresponding":false},{"id":449565,"name":"Ragini R. Kudchadkar","orcid":"0000-0001-9070-5052","position":10,"is_corresponding":false},{"id":314034,"name":"Hannah M. Knochelmann","orcid":"0000-0003-0644-123X","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:27:06.198948Z","pmid":"35433480","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}