Incidence and risk of musculoskeletal and rheumatologic (MSK-R) immune-related adverse events (irAEs) in a large real-world cohort.

Abstract

e23409 Background: Immunotherapy (IT) improves cancer outcomes but is associated with irAEs, including MSK-R toxicities, which occur in 5–10% of patients, predominantly as arthralgias & myalgias, & may impair quality of life or lead to treatment interruption. Real-world comparative data on incidence & risk across tumor types remain limited. We evaluated the incidence & risk of MSK-R irAEs in patients receiving IT versus chemotherapy alone. Methods: We conducted a retrospective cohort study of adult cancer patients (n = 5,556) treated between 2010–2022 at Cleveland Clinic Ohio centers. Patients (≥18 years) with cancers eligible for first-line IT were included. Patients receiving IT (± chemotherapy ± radiation) were compared with those not receiving IT. Follow-up began at systemic therapy initiation & continued until irAE occurrence, last follow-up, or death. MSK-R irAEs included inflammatory arthritis, myositis, polymyalgia rheumatica, keratitis, salivary gland dysfunction, & vasculitis; arthralgia & myalgia were excluded. Data on attribution, CTCAE grade, management, IT interruption or rechallenge, & outcomes were collected. Incidence rates per 100 person-years were calculated using Poisson methods. Cumulative incidence (CIR) was estimated with Kaplan-Meier methods. Adjusted hazard ratios (HRs) were estimated using time-dependent Cox models treating IT exposure as a time-varying covariate. Results: Among the cohort, 1,291 (23%) & 948 (17%) received first- & second-line IT. Median age was 66 years; 38% were female & 87% were White. Anti-PD-1/PD-L1 &/or anti–CTLA-4 agents accounted for 99.9% of IT exposure. The cohort was dominated by advanced lung cancer, particularly stage IV non-small cell lung cancer (29%), followed by esophageal/gastric (stages II–III: 14%; stage IV: 11%) and other advanced solid tumors. During median follow-up of 14 months (CI: 6-34), 46 MSK-R irAEs were observed, including 23 events among patients receiving first-line IT. Incidence rates were higher in IT than non-IT group (0.09 vs 0.02 per 100 person-years; P < 0.05). Inflammatory arthritis accounted for most events (0.06 vs 0.01 per 100 person-years). The 24-month CIR of MSK-R irAEs was 2.3% with IT vs 0.6% in non-IT (log-rank P < 0.01; HR 7.1; P < 0.01). The 24-month CIR of inflammatory arthritis was 1.7% versus 0.2% (P < 0.01). Among inflammatory arthritis cases, 72% were CTCAE grade II–III; immunomodulatory therapy was used in 65%, mainly corticosteroids, with an 89% response rate. Conclusions: In this large real-world cohort, IT was associated with a substantially increased risk of MSK-R irAEs, driven primarily by inflammatory arthritis, although events were uncommon, consistent with prior reports. These toxicities often required immunosuppressive therapy and were associated with IT interruption or discontinuation, underscoring the need for multidisciplinary management.