Overview of checkpoint inhibitor pneumonitis: incidence and associated risk factors

ABSTRACT

Introduction: The development of immune checkpoint inhibitors (ICIs) has been a breakthrough in the treatment of several types of cancer. With the widespread use of ICIs in clinical practice, checkpoint inhibitor pneumonitis (CIP) is expected to increase and its management will pose a challenge for clinicians.

Areas covered: In this article, we review the incidence, associated risk factors, radiological patterns, clinical features, and management of CIP.

Expert opinion: Several clinical trials assessing the efficacy and safety of combination treatments with various drugs and ICIs have been conducted. From the results of these trials, CIP is thought to be an acceptable side effect because the frequency of its development was slightly higher during combination therapies than during ICI monotherapies. However, the risk of developing CIP associated with combinations of chemotherapy and ICIs may be higher in the real world than in clinical trials. Because combinations of chemotherapy and ICIs are associated with increased toxicity, the proper management of immune-related adverse events is necessary to maximize the efficacy of the treatment.

KEYWORDS:

• Non-small-cell lung cancer
• immune checkpoint inhibitor (ICI)
• immune-related adverse events (irAEs)
• checkpoint inhibitor pneumonitis

Article highlights

• Checkpoint inhibitor pneumonitis (CIP) is one of the immune-related adverse events (irAEs) that can lead to fatal respiratory failure.

• Careful consideration should be given to the suitability of ICIs for patients with risk factors for CIP, especially those with preexisting lung disease.

• The actual occurrence of CIP associated with the immune checkpoint inhibitors (ICIs) monotherapy and the ICIs combined with other drugs may be higher in real-world practice than in those reported in clinical trials.

• The use of combination therapies may increase the risk of CIP in exchange for a better anticancer response, so appropriate management is necessary to maximize their efficacy.

This box summarizes key points contained in the article.

Declaration of interest

Y Shibata has received honoraria from Pfizer, Bristol-Myers Squibb, AstraZeneca, and Taiho Pharmaceutical. S Murakami has received honoraria from AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, and Ono Pharmaceutical. T Kato has received grants and/or personal fees from, and/or has played consulting/advisory roles for Abbvie, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eli Lilly and Company, Kyorin, Kyowa Hakko Kirin, Merck Serono, MSD, Nitto Denko, Novartis, Ono, Pfizer, Regeneron, Sumitomo Dainippon, Taiho, and Takeda. 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 disclosures

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

Additional information

Funding

The preparation of this paper received no funding.