Rheumatic adverse events of immune checkpoint inhibitors in cancer immunotherapy

ABSTRACT

Introduction

The advent of immune checkpoint inhibitors (ICIs) in cancer treatment has marked a transformative era, albeit tempered by immune-related adverse events (irAEs), including those impacting the musculoskeletal system. The lack of precise epidemiologic data on rheumatic irAEs is attributed to factors such as potential underrecognition, underreporting in clinical trials, and the tendency to overlook manifestations without immediate life-threatening implications, further complicating the determination of accurate incidence rates, while the complete understanding of the mechanisms driving rheumatic irAEs remains elusive.

Areas Covered

This literature review comprehensively examines rheumatic irAEs in cancer patients undergoing ICI therapy, encompassing epidemiology, risk factors, mechanisms, clinical manifestations, and current management guidance for prevalent conditions such as inflammatory arthritis, polymyalgia rheumatica, and myositis. Less frequent rheumatic and musculoskeletal irAEs are also explored, alongside insights into ongoing clinical trials testing therapeutic and preventive strategies for irAEs. A thorough literature search on Medline and the National Cancer Institute Clinical Trials Database was conducted up to October 2023 to compile relevant information.

Expert Opinion

In light of the evolving landscape of cancer immunotherapy, there is a compelling need for prospective longitudinal studies to enhance understanding and inform clinical management strategies for rheumatic irAEs.

KEYWORDS:

• Cancer
• immune checkpoint inhibitors
• rheumatic diseases
• immune-related adverse events (irAEs)
• inflammatory arthritis
• polymyalgia rheumatica
• myositis

Article highlights

• Immune checkpoint inhibitors (ICIs) can elicit a diverse array of rheumatic immune-related adverse events (irAEs), with a higher incidence seen in patients undergoing anti-programmed cell death-1/programmed cell death-ligand 1 therapy or combined ICI regimens.

• Inflammatory arthritis and polymyalgia can occur at any time during the course of ICI treatment. They can be chronic necessitating longterm treatment. With adequate treatment it may be possible for patients to continue ICI therapy.

• Myositis is a severe irAE that can present as a clinical triad with co-existing myocarditis and myasthenia gravis, which carries a serious prognosis with high case fatality rates.

• An understanding of the true incidence, characteristics, severity, pathogenesis, and outcome of rheumatic irAEs will require collaborative multicenter efforts.

• Clinical trials including prospective systematic collection of longitudinal blood and tissue samples are important to unveil the underlying immunobiology, identify predictive markers, and customize treatment strategies on an individualized basis.

Declaration of interest

N Abdel-Wahab has a K01 Mentored Research Scientist Development Award from the National Institute of Allergy and Infectious Diseases (K01AI163412) and received the University of Texas MD Anderson Cancer Center Institutional Research Grant, Division of Internal Medicine Development Award, Survivorship Seed Money Award, Prioritizing Research Innovation and Mentoring Excellence Award, and the U.T. MD Anderson SPORE in Melanoma Career Enhancement Program Award (P50CA221703). M Suarez-Almazor has received consulting fees in the past 12 months from Pfizer, Eli Lilly, Syneos Health and Celgene, all unrelated to this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

We thank S Yadugiri, the Senior Technical Writer in the Department of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center, for editorial support.

Additional information

Funding

This paper was funded by K01 Mentored Research Scientist Development Award from the National Institute of Allergy and Infectious Diseases [K01AI163412].