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

Background: Immune checkpoint inhibitors (ICIs) are first-line treatment for melanoma. The incidence of musculoskeletal immune-related adverse events (MSK irAEs) remains unclear.

Objective: 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.

Methods: 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.

Results: Four RCTs met the inclusion criteria (n = 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.

Conclusions: 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.

Implications for practice: MSK irAEs can impact quality of life and should be considered, particularly in the adjuvant setting when risks and benefits are carefully weighed.