Rheumatologic immune-related adverse events (irAE) in patients (pts) with genitourinary (GU) malignancies treated with immune checkpoint inhibitors (CPI).

Abstract

652 Background: Rheumatologic irAEs in pts treated with CPIs present a clinical challenge. We describe the clinical characteristics, treatment, and outcomes of rheumatologic irAEs in CPI-treated GU malignancy pts. Methods: Pts with GU malignancies 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 analyzed. Results: Twenty-three pts were identified; 19 (83%) had renal cell carcinoma (RCC) and 4 (17%) had urothelial carcinoma (UC). The majority (70%) were male; median age at diagnosis was 56 (range, 36-78). All RCC pts had clear cell histology and all had prior nephrectomy; 1 UC pt had prior cystectomy. Most RCC pts (58%) received antiangiogenic therapy prior to CPI treatment and 50% of UC pts received prior chemotherapy. CPI therapy included anti-PD-L1 (30%), anti-PD-1 (43%), and combined PD-1 / CTLA-4 antibodies (26%). Median time from CPI initiation to rheumatologic irAE was 5.1 months (range, 0.23 – 51.3). Most (74%) patients had 2-4 muscle or joint groups involved. CPI was held in in 20 (87%) pts who developed rheumatologic irAEs. Most (96%) pts were treated with prednisone. Median initial prednisone dose was 40mg/d (range, 10-90mg/d) and median duration of prednisone therapy was 43.6 weeks (range, 2.5–206). Treatment intensification with methotrexate (14%), infliximab (14%), tocilizumab (9%), and etanercept (9%) was required in some pts for rheumatologic symptom control. Of the patients whose CPI was held for rheumatologic irAEs, 30% restarted CPI therapy following symptoms improvement, 15% switched to a subsequent therapy, and 55% have an ongoing sustained response to therapy (median 9.1 months; range, 0.63 - 46.1) despite no subsequent anti-cancer therapy. Conclusions: Rheumatologic irAEs in CPI-treated GU malignancy pts vary in timing of presentation, severity, and treatment. Multidisciplinary teams that include a rheumatologist are critical for optimal pt management. Larger pt populations are needed to assess the predictive/prognostic impact of these irAEs on outcome.