Skill Checkup: A 48-Year-Old Triple-Negative Breast Cancer Patient Falls Ill During Immune Checkpoint Inhibitor Therapy

Kelly E. McCann, MD, PhD


May 24, 2022

On the basis of the described regimen of chemotherapy with immune checkpoint inhibitor (ICI) therapy, it is likely that this patient is presenting with pneumonitis as an immune-related adverse event (IRAE). In the course of manipulating the immune system to induce antitumor response, ICIs can set off a distinct set of adverse reactions, and considering their immune-based nature, these reactions differ from standard chemotherapy toxicities. Taxane-induced pneumonitis tends to present within days to weeks, with less pneumonitis seen with nabpaclitaxel than paclitaxel or docetaxel. The majority of IRAE effects are mild to moderate, but severe and even fatal adverse events can also arise; therefore, IRAEs should be identified and treated early, with multidisciplinary management usually required. Pneumonitis is one of the most common causes of ICI-related death, with acute interstitial pneumonitis and diffuse alveolar damage syndrome representing the most acute life-threatening event in this setting. Although life-threatening IRAEs of all types are uncommon, clinical suspicion should be heightened, as they may mimic other more established conditions, such as preexisting PF, chronic obstruction pulmonary disease, and atypical pneumonia.

Compared with adverse events stemming from chemotherapy, IRAEs typically develop later but last longer, owing partially to pharmacodynamic differences. Pneumonitis can develop at any time during treatment, even after discontinuation, but patients with ICI-related pneumonitis usually present later than other IRAEs, at several months after treatment initiation. The condition is the most common pulmonary toxicity of ICI therapy, though its overall incidence is low among patients with breast cancer. The estimated incidence of pneumonitis associated with programmed cell death protein 1/PDL-1 and cytotoxic T lymphocyte-associated antigen-4-targeted therapies is < 5%, with high-grade (≥ grade 3) events occurring in 1%-2% of patients. However, the reported incidence of pneumonitis is increasing, as therapeutic indications and regimens for ICIs evolve for advanced breast and other cancers.


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