Melanoma patients have persistent side effects after immunotherapy

Skin cancers

By Mardi Chapman

16 Aug 2023

A significant proportion of patients who develop immune-related adverse events (irAEs) with immune checkpoint inhibitor therapy for melanoma will have prolonged symptoms sometimes lasting for years.

An Australian and US study, published in JAMA Network Open [link here], found endocrine toxic effects such as adrenal insufficiency, hypophysitis, and thyroiditis or hypothyroid were the most likely to become chronic.

The study comprised ≥18 months follow-up of 318 patients treated with adjuvant anti–PD-1 therapy for advanced and metastatic melanoma between 2015 and 2020.

Most patients (71%) experienced acute irAEs – defined as arising during their treatment – including dermatitis or pruritus (28.6%), thyroiditis or hypothyroid (15.4%), arthritis or arthralgias (14.5%), and colitis or diarrhoea (10.4%).

Most were ≥ grade 2 (64%) and 50% required steroid treatment.

Delayed irAEs, arising within 6 months of treatment cessation, were reported in 17% of patients.

The study found chronic irAEs, persisting at least 3 months after treatment cessation, occurred in 46% of patients.

The investigators said adrenal insufficiency (80.0%), hypophysitis (100.0%), thyroiditis/hypothyroid (85.7%), neuropathy (85.7%), and nephritis (80%) appeared particularly likely to evolve into chronic irAEs.

Other relatively common chronic irAEs included bullous pemphigoid (67%), xerostomia (56%) and ocular toxic effects (57%).

Colitis or diarrhoea (12.5%), dermatitis or pruritus (22.1%), hepatitis (18.2%), and pneumonitis (44.4%) had lower rates of chronicity.

The study said 38.1% of patients required treatment with corticosteroids for chronic toxic effects.

The median time to resolution of chronic irAEs was 19.7 months from the time of anti–PD-1 start and 11.2 months from the time of anti–PD-1 cessation; 63% of patients with chronic irAEs had persistent symptoms for more than two years.

The study also noted that patients with chronic irAEs had less disease recurrence than those without (33% v 45%).

“The persistent nature of irAEs, particularly endocrinopathies, suggests that permanent damage may occur in some patients,” the study said.

“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,” it concluded.

Australian investigators on the study included Professor Georgina Long, Associate Professor Matteo Carlino and Associate Professor Alexander Menzies from the Melanoma Institute Australia.

Already a member?

Login to keep reading.

Email me a login link