Does Autoimmune Disease Affect AE Rate With Immune Checkpoint Inhibition for Melanoma?

This PD-1 inhibitor is effective for treating melanoma, though it can be highly toxic and there is a
This PD-1 inhibitor is effective for treating melanoma, though it can be highly toxic and there is a
The safety and efficacy of immune checkpoint inhibition in patients with advanced melanoma with and without autoimmune disease was assessed.

Although patients with melanoma and preexisting autoimmune disease (AID) have historically been excluded from clinical trials of immune checkpoint inhibition (ICI) because of the risk for immune-related adverse events (irAEs), a new study suggests there is no difference in patients with vs without preexisting AID in regard to the overall incidence of any ICI-associated irAE. Findings from this study were published in the Annals of Internal Medicine.

This study included 4367 patients with advanced melanoma who were enrolled in the Netherlands’ Dutch Melanoma Treatment Registry from2013 to 2018. All patients were followed through February 2019. Approximately 9.5% (n=415) of patients had AID, including rheumatologic AID (n=227), endocrine AID (n=143), inflammatory bowel disease (IBD) (n=55), or other (n=8). The investigators of this study evaluated irAEs of grade 3 or higher, treatment response, and survival outcomes in relation to the use of ICI.

A total of 228 patients with AID (55%) were treated with ICI vs 2546 (58%) patients without AID. Treatments included anti-cytotoxic T lymphocyte–associated protein 4 (CTLA-4) in 87 patients, anti-programmed cell death 1 (PD-1) in 187 patients, and a combination of CTLA-4 and PD-1 in 34 patients.

In patients with AID, the incidence rates of irAEs of grade 3 or higher were 30% (95% CI, 21-41) with anti–CTLA-4, 17% (95% CI, 12-23) with anti–PD-1, and 44% (95% CI, 27-62) with a combination of the 2 ICI approaches. In contrast, the incidence rates for irAEs in patients without AID were 30% (95% CI, 27-33) for anti–CTLA-4, 13% (95% CI, 12-15) for anti–PD-1, and 48% (95% CI, 43-53) for combined ICIs.

A higher percentage of anti–PD-1 treatment discontinuations due to toxicity was reported in patients with AID (17% vs 9%). Patients who had a diagnosis of IBD more often experienced colitis caused by anti–PD-1 (19%) vs patients with other AIDs (3%) and patients without AID (2%).

Limitations of this study included the lack of robust information on patients’ immunosuppressive therapies as well as the lack of data on overall AID severity.

Although patients with IBD may require greater monitoring if on ICI, the investigators of this study wrote that they “encourage physicians not to withhold ICI in most common AIDs.”


van der Kooij MK, Suijkerbuijk KPM, Aarts MJB, et al. Safety and efficacy of checkpoint inhibition in patients with melanoma and preexisting autoimmune disease: A cohort study. Ann Intern Med. Published online February 16, 2021. doi:10.7326/M20-3419