Disclosures: van der Kooij reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
February 15, 2021
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Checkpoint inhibitor response, adverse event rate similar regardless of autoimmune disease

Disclosures: van der Kooij reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Patients’ response to anti-CTLA-4 or anti-PD-1 checkpoint therapy for advanced melanoma, and their incidence of immune-related adverse events of grade 3 or higher, were similar regardless of preexisting autoimmune disease, according to data.

However, researchers writing in the Annals of Internal Medicine noted that severe colitis and toxicity requiring early discontinuation did occur more frequently in participants with preexisting inflammatory bowel disease.

“We encourage physicians not to withhold ICI in most common AIDs,” Monique K. van der Kooij, MD, and colleagues wrote. “However, close monitoring in patients with IBD is advised because the incidence of severe colitis and early discontinuation of treatment due to toxicity was higher in this group.” Source: Adobe Stock

Immune checkpoint inhibition (ICI) has greatly improved survival of patients with advanced (that is, unresectable stage 3 or 4) melanoma,” Monique K. van der Kooij, MD, of Leiden University Medical Center, in the Netherlands, and colleagues wrote. “Both anti–cytotoxic T lymphocyte–associated protein 4 (CTLA-4) and anti–programmed cell death 1 (PD-1) have been approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of melanoma.”

“The number of indications is rapidly expanding to other solid and hematologic tumors, so more patients with cancer will potentially benefit from these therapies,” they added. “However, its use can be hampered by serious immune-related adverse events (irAEs) that mimic classic autoimmune diseases (AIDs). Trials studying ICI have excluded patients with preexisting AIDs because of concerns about unleashing their underlying autoimmunity. Case reports typically describe unique manifestations and are not generalizable to the population at large, which has limited recently published reviews.”

To examine the safety and efficacy of immune checkpoint inhibitors for advanced melanoma among patients with and without autoimmune disease, van der Kooij and colleagues conducted a nationwide cohort study of 4,367 participants in enrolled in the Dutch Melanoma Treatment Registry. Patients included in the study were those enrolled between July 2013 and July 2018, and followed through February 2019.

For their study, van der Kooij and her colleagues analyzed patient, clinical and treatment data, as well as the incidence of immune-related adverse events of grade 3 or higher, treatment response and survival. In all, 415 of the included patients demonstrated autoimmune disease. Among these participants, 227 had rheumatic autoimmune diseases, 143 had endocrine autoimmune conditions and 55 had inflammatory bowel disease. The remaining eight were classified as “other.”

A total of 228 patients with autoimmune disease, and 2,546 without autoimmune conditions, received immune checkpoint therapy. For patients with autoimmune disease treated with checkpoint therapy, 87 received anti-CTLA-4 and 187 received anti-PD-1, while 34 were given a combination. For those without autoimmune disease treated with checkpoint inhibitors, 916 received anti–CTLA-4, 1,540 received anti-PD-1, and 388 were administered combination therapy.

According to the researchers, the incidence rates for immune related adverse events of grade 3 or higher in patients with autoimmune disease were 30% (95% CI, 21% to 41%) with anti–CTLA-4, 17% (95% CI, 12% to 23%) with anti PD-1, and 44% (95% CI, 27% to 62%) with combination therapy. Meanwhile, rates for those without autoimmune disease were 30% (95% CI, 27% to 33%), 13% (95% CI, 12% to 15%) and 48% (95% CI, 43% to 53%), respectively.

Patients with autoimmune disease discontinued anti–PD-1 treatment due to toxicity at a rate of 17% (95% CI, 12% to 23%), compared with 9% for patients without these diseases (95% CI, 8% to 11%). Patients with inflammatory bowel disease were more prone to anti–PD-1 induced colitis — with a rate of 19% (95% CI, 7% to 37%) — compared with participants with other autoimmune diseases — 3% (95% CI, 0% to 6%) — and those without autoimmune disease — 2% (95% CI, 2% to 3%).

Objective response rates were similar across patients with and without autoimmune disease treated with anti–CTLA-4 — 10% (95% CI, 5% to 19%) compared with 16% (85% CI, 14% to 19%), respectively — and anti–PD-1 — 40% (95% CI, 33% to 47%) compared with 44% (95% CI, 41% to 46%), respectively. For combination therapy, objective response rates were 39% (95% CI, 20% to 59%) and 43% (95% CI, 38% to 49%) for participants with and without autoimmune disease, respectively. Survival did not differ between patients with and without autoimmune disease.

“We show that tumor response to ICI treatment with anti–CTLA-4, anti–PD-1, or their combination for advanced melanoma and incidence of irAEs of grade 3 or higher were similar in patients with and without preexisting AID of rheumatologic or endocrine origin in daily clinical practice,” van der Kooij and colleagues wrote. “Therefore, we encourage physicians not to withhold ICI in most common AIDs. However, close monitoring in patients with IBD is advised because the incidence of severe colitis and early discontinuation of treatment due to toxicity was higher in this group.”