Anti-PD-1 Therapy for Melanoma Associated With Chronic Immune-Related Adverse Events

To assess the incidence, characteristics, and long-term outcomes of chronic immune-related adverse events (irAEs) caused by adjuvant anti-programmable cell death-1 (anti-PD-1) therapy, researchers conducted a retrospective, multicenter cohort study and found that irAEs were common and affected multiple organ systems.¹

Goodman et al collected data from 6 academic medical centers in the United States and Australia. Patients who received at least 1 dose of adjuvant anti-PD-1 therapy with at least 18 months of follow-up were included. Acute irAEs were those that arose during treatment, delayed irAES arose within 6 months of treatment cessation, and chronic irAEs were those that continued at least 3 months after treatment cessation.

Median age of the 318 patients in the study was 64 years and 59.7% were male. Patients were treated with adjuvant anti-PD-1 therapy for advanced and metastatic melanoma. Nivolumab was given to 255 (80.2%) patients andpembrolizumab was given to 63 (19.8%) patients. The median duration of treatment was 315 days.

Of the 318 patients, 226 developed acute irAEs and 53 developed delayed toxic events. Most acute irAES were grade 2 or higher (144 patients) and 114 required steroids. Dermatitis or pruritis (28.6%), thyroiditis or hypothyroid (15.4%), arthritis or arthralgias (14.5%), and colitis or diarrhea (10.4%) were the most common acute irAEs.

Acute irAEs, including delayed irAEs, that were likely to become chronic were adrenal insufficiency, hypophysitis, thyroiditis/hypothyroid, neuropathy, and nephritis.

Of the 318 patients, 147 (46.2%) developed chronic toxic effects, with 74 of those patients experiencing at least a grade 2, and 6 of those patients experiencing a grade 3 to 5. Of the patients who developed chronic toxic effects, 56 (38.1%) required corticosteroids. One hundred patients (68%) experienced symptomatic chronic toxic effects.

Of the 75 patients with acute endocrine irAEs, 64 (85.3%) became chronic, and 11 of those also had nonendocrine irAEs.

Resolution of chronic irAEs at last follow-up occurred for 54 of 147 patients (36.7%) with extended follow-up (median, 1057 days). Of the 147 with chronic toxic effects, 93 (63.3% of the cohort) had ongoing effects. Chronic irAEs resolved in 14.4 to 31.5 months from the initiation of anti-PD-1 and 8.1 to 20.7 months from the cessation of anti-PD-1 therapy.

Of 93 patients with persistent toxic effects at last follow-up, 55 (17.3% of original cohort) were grade 2 or higher and 41 (12.9% of original cohort) continued to be symptomatic. The majority of persistent irAEs were hypothyroid (40.9%), adrenal insufficiency (8.6%), arthritis (19.4%), dermatitis or pruritis (.7%), and hypophysitis (8.6%).

Of the 6 patients with chronic grade 3 to 5 irAEs, 3 showed improvement by last follow-up, 2 continued to have ongoing irAEs at last follow-up, and 1 had resolved.

Endocrine toxic effects were more likely to become chronic and continue at last follow-up than nonendocrine toxic effects, but other more symptomatic irAEs persisted at low rates individually, including cutaneous, rheumatologic, oral, and ocular events.

Goodman et al concluded that “Insights into the long-term impact of adjuvant anti–PD-1 therapy are crucial to optimize patient outcomes as these agents are used across different tumor types. The high prevalence of chronic irAEs suggests the importance of considering the risk-benefit ratio when initiating adjuvant therapy and the need for prolonged monitoring and proactive management of irAEs.”

This article originally appeared on Dermatology Times.

Reference

1. Goodman RS, Lawless A, Woodford R, et al. Extended follow-up of chronic immune-related adverse events following adjuvant anti–PD-1 therapy for high-risk resected melanoma. JAMA Netw Open. 2023;6(8):e2327145. doi:10.1001/jamanetworkopen.2023.27145