Epidemiology, risk factors and outcomes of rheumatic toxicities of immune checkpoint inhibitors in patients with advanced melanoma

Aim  To estimate the frequency of rheumatic toxicities of immune checkpoint inhibitors (ICI) in patients with advanced melanoma and to identify risk factors and potential predictors of outcomes.  Method  A single-centre observational study of patients with stage III or IV melanoma receiving all available ICI therapies, who completed a for-purpose questionnaire to capture rheumatic symptoms upon recruitment and at 12-months. Clinical details were extracted from patients’ medical records. Potential predictors of rheumatic toxicities and cancer outcomes were identified through regression analysis.  Results  Amongst 147 eligible patients, the prevalence of new or worsening rheumatic symptoms was 32.5% at recruitment and 21% at 12 months. The incidence of documented arthralgia, inflammatory arthritis and PMR-like syndrome were 39.5%, 5.4% and 3.4% respectively. Binary logistic regression identified pre-existing symptomatic rheumatic disease, including non-immune mediated rheumatic disease, as the primary risk factor for developing rheumatic toxicities (OR 3.16, 95% CI 1.36 – 7.34). Continuation of ICI therapy (OR 16.5, 95% CI 2.53 – 107.70), followed by rheumatic toxicities (OR = 14.2, 95% CI 1.45 – 138.62) were variables associated with favourable tumour response.  Conclusion  Rheumatic toxicities of ICI therapy commonly affect patients with melanoma and are more likely to occur in patients with pre-existing autoimmune and non-immune mediated rheumatic disease, especially when symptomatic prior to commencing treatment. Rheumatic toxicities are associated with favourable tumour responses.