Rheumatic Immune-Related Adverse Events in Patients with Metastatic Melanoma: Insights for Treatment from a Single Cancer Center

Abstract Clinical trials that led to the Food and Drug Administration (FDA) approval of systemic cancer therapies have generally excluded patients with autoimmune disease (AID) due to concerns about increased immune-related adverse events (irAEs), disease flares, and potential reductions in the efficacy of immunotherapies. To evaluate the optimal disease-modifying antirheumatic drug (DMARD) for patients with metastatic melanoma and immune-mediated rheumatic disease based on a narrative literature review and a case series from A.C.Camargo Cancer Center. This retrospective study included 10 adults with disseminated melanoma and immune-mediated diseases who were treated at the Rheumatology Outpatient Clinic at A.C.Camargo Cancer Center in Brazil between January 2020 and September 2024. A narrative literature review was conducted utilizing the Scopus and PubMed databases. In this case series, 6 of the total 10 patients were treated with methotrexate (MTX), while those needing enhanced immunosuppression received tocilizumab due to its dual antitumor and anti-inflammatory properties. Furthermore, combining it with BRAF/MEK inhibitors effectively controlled inflammatory symptoms in the joints and skin. Clinical trials indicated that MTX and anti-IL-6 therapies are safe and effective in preventing and treating irAEs induced by immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors. Previous case series suggest hydroxychloroquine and anti-IL-17 therapies may also be viable options. However, abatacept, sulfasalazine, and leflunomide should be avoided in patients receiving ICIs. When selecting an appropriate DMARD, the potential synergistic or detrimental effects on tumor behavior, the patient's risk for adverse events, melanoma stage, and ongoing cancer treatment should all be considered. Individual cytokine profiles and specific immune cell types may direct future research for managing irAE. Additionally, the degree of immunosuppression experienced by a patient may significantly impact their prognosis and warrants further investigation.