Long-Term Toxicities of Immune Checkpoint Inhibitor (ICI) in Melanoma Patients

Curr Oncol. 2022 Oct 20;29(10):7953-7963. doi: 10.3390/curroncol29100629.

Abstract

ICI therapy has greatly improved patient outcomes in melanoma, but at the cost of immune-related adverse events (irAEs). Data on the chronicity of irAEs, especially in real-world settings, are currently limited. We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥ 6 months), transient (resolution over a period < 6 months), or no irAEs. A total of 283 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, fifteen (9.3%) experienced long-term irAEs as their longest-lasting toxicity, thirty-four (21.1%) developed transient irAEs only, and forty-six (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (36.0%) or skin-related (32.4%). Grade 3-4 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still requiring treatment for long-term or permanent irAEs 6 months or more following the completion of ICI therapy, including twenty-four patients on thyroid hormone replacement and twenty-two on oral steroids. ICI treatment was temporarily interrupted for 64 (22.6%) irAEs and permanently discontinued due to irAEs in 38 patients (13.6% of irAEs, 23.6% of patients); additionally, 4 (2.5%) patients died of irAEs. Our findings show that ICI treatment in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients, which should therefore be discussed when obtaining consent for treatment.

Keywords: immune checkpoint inhibitor; immunotherapy; melanoma; oncology.

MeSH terms

  • Adult
  • Antineoplastic Agents, Immunological* / adverse effects
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Melanoma* / chemically induced
  • Melanoma* / drug therapy
  • Retrospective Studies
  • Syndrome
  • Thyroid Hormones / therapeutic use

Substances

  • Immune Checkpoint Inhibitors
  • Antineoplastic Agents, Immunological
  • Thyroid Hormones

Grants and funding

This research received no external funding.