Rheumatologic immune-related adverse events (irAE) in patients treated with checkpoint inhibitors (CPI) are not well characterized. We present the characteristics, treatment, and outcomes of rheumatologic irAEs in CPI-treated metastatic renal cell carcinoma (mRCC) patients.

Patients with mRCC who were treated with CPIs and developed grade ≥ 2 (per CTCAEv4) rheumatologic irAEs (i.e., arthralgias and myalgias) were retrospectively reviewed. Patient-, disease-, and rheumatologic-related data were collected and summarized as frequency counts and percentages, or medians and ranges.

Nineteen patients were identified. The majority of patients (68%) were male; median age at diagnosis was 54 (range, 48-65). All patients had clear cell histology, all had prior nephrectomy, and 53% were intermediate risk by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. Most (58%) patients received antiangiogenic therapy prior to CPI treatment. CPI therapy included anti-PD-L1 (26%), anti-PD-1 (42%), and combined PD-1 / CTLA-4 antibodies (32%). Median time from CPI initiation to rheumatologic irAE was 5.5 months (range, 0.23 – 51.3). Most (68%) patients had 2-4 muscle or joint groups involved. CPI was held in in 17 (89%) patients who developed rheumatologic irAEs. All patients were treated with prednisone. Median initial prednisone dose was 40mg/d (range, 10-60mg/d) and median duration of prednisone therapy was 45.3 weeks (range, 2.6–206). Treatment intensification with methotrexate (16%), infliximab (16%), tocilizumab (11%), and etanercept (11%) was required in some patients for rheumatologic symptom control. Of the patients whose CPI was held for rheumatologic irAEs, 24% restarted CPI therapy following symptoms improvement, 18% switched to a subsequent mRCC therapy, and 59% have an ongoing sustained response to therapy (median 10.2 months; range, 0.63 – 46.1) despite no subsequent treatment for mRCC.

Rheumatologic irAEs in CPI-treated mRCC patients vary in timing of presentation, severity of symptoms, and treatment. These patients are best treated in multidisciplinary teams that include a rheumatologist. The prognostic and predictive impact of these irAEs needs to be assessed in a larger patient population.