Musculoskeletal immune-related adverse events of PD-(L)1 inhibitors in melanoma: a systematic review and meta-analysis

Immune checkpoint inhibitors (ICIs) are first-line treatment for melanoma. The incidence of musculoskeletal immune-related adverse events (MSK irAEs) remains unclear. To estimate the relative risk of MSK irAEs in melanoma patients treated with ICIs targeting programmed cell death-1 or its ligand PD-(L)1 as compared to placebo. We performed a systematic literature review including phase III randomized controlled trials of adult melanoma patients comparing a PD-(L)1 inhibitor to a placebo arm. Outcomes of interest included arthralgias, arthritis, back pain and myalgias. Meta-analysis was performed to estimate the pooled relative risk of MSK irAEs over the treatment course. Four RCTs met the inclusion criteria (<i>n</i> = 3,041 subjects). Use of PD-(L)1 inhibitors was associated with an increased risk of developing arthralgias (RR 1.30 [95% CI: 1.13–1.49]) and myalgias (RR 1.48 [95% CI: 1.17–1.87]) as compared to placebo. Back pain and arthritis were not reported. Use of PD-(L)1 inhibitors is associated with a significantly increased risk of arthralgias and myalgias in melanoma patients. The risk of back pain and arthritis is unknown. MSK irAEs can impact quality of life and should be considered, particularly in the adjuvant setting when risks and benefits are carefully weighed.