Impact of bone metastases on outcomes in patients with metastatic melanoma treated with immune checkpoint inhibitors

We evaluated the management and outcomes of patients with unresectable melanoma with and without bone metastases treated with single-agent or combination immune checkpoint inhibitors. We performed a retrospective chart review of unresectable or metastatic melanoma patients treated with immunotherapy at Sunnybrook Health Sciences Centre between June 2012 and November 2025. Patients were stratified by bone metastases and treatment regimen. Single-agent ipilimumab recipients were excluded from survival analyses. Overall survival (OS) was analyzed using Kaplan–Meier methods, with multivariable Cox regression evaluating associations of bone metastases and treatment type. We identified 490 patients: median age 68.0 years, 38.6% female, and 36.3% BRAF V600E/K-mutant. Bone metastases occurred in 27.6%, of whom 3.7% received bisphosphonates. With combination immunotherapy, median OS was 17.8 months [95% confidence interval (CI) = 11.0–30.9] with bone metastases ( n  = 33) and 31.2 months (95% CI = 24.3–35.3) without ( n  = 110). With single-agent immunotherapy, median OS was 16.8 months (95% CI = 13.5–24.9) with bone metastases ( n  = 75) and 28.7 months (95% CI = 24.8–37.8) without ( n  = 208). Toxicity-related discontinuation occurred in 47.6% with combination and 28.0% with single-agent immunotherapy. OS differed significantly across groups (log-rank P  = 0.0048). On multivariable analysis, bone metastases independently predicted worse OS (hazard ratio = 1.58, 95% CI = 1.25–2.00, P  < 0.001), while immunotherapy regimen did not (hazard ratio = 0.92, 95% CI = 0.71–1.19, P  = 0.521). Bone metastases were independently associated with poor OS in metastatic melanoma, with no difference between combination and single-agent immunotherapy. Given the higher toxicity of combination therapy and limited bisphosphonate use, further evaluation of treatment strategies is warranted.