Abstract
Background Immune checkpoint inhibitors (ICI) have changed the landscape in the treatment of a number of cancers. Immune-related adverse events (irAEs) have emerged as a serious clinical problem with the use of ICI. Methods All oncology patients diagnosed with pulmonary complications secondary to ICI at Mayo Clinic Rochester from January 1, 2012 to December 31, 2018 were reviewed. Demographics, comorbidities, smoking, and oncologic history were analyzed. Results A total of 10 patients developed pulmonary complications secondary to ICI. Seven patients were men (70%), and the median age at diagnosis was 61.5 (IQR 55.8-69.3) years. All patients had stage IV disease. Melanoma was the most common malignancy. Seven (70%) patients had a positive smoking history, and 6 (60%) were obese (BMI > 30). Most cases were grade 2 pneumonitis (70%). One patient with grade 4 pneumonitis required endotracheal intubation and a prolonged course of systemic corticosteroids (>30 days). Eight (80%) patients received prior radiation therapy. The median time from initiation of ICI to pneumonitis diagnosis was 3.5 months. Conclusion Melanoma was the most common malignancy, the majority of patients had grade 2 pneumonitis and required treatment with steroids, and all patients affected by ICI-related pneumonitis had stage IV malignancy. Potential risk factors included smoking history, prior radiotherapy, obesity, and advance stage at the time of ICI initiation. Extrapulmonary irAEs are common in patients with pneumonitis.
Highlights
Programmed death 1 (PD-1) and its ligands (PD-L1 and PD-L2), in addition to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), are negative regulators of T-cell activation that play an integral role in immune homeostasis [1, 2]
Evidence shows that immune checkpoint inhibitor (ICI) use is associated with increased risk of all-grade pneumonitis compared with other conventional chemotherapeutic agents [6]
Pulmonary Immune-related adverse event small cell lung cancer (SCLC) (irAE) are of special interest because they can lead to intensive care unit (ICU) admission, endotracheal intubation, and in severe cases, death
Summary
Programmed death 1 (PD-1) and its ligands (PD-L1 and PD-L2), in addition to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), are negative regulators of T-cell activation that play an integral role in immune homeostasis [1, 2]. With the development of these novel agents came a new group of distinctive immune adverse reactions, thought to be related to cytokine release, that range from transient and benign to severe and fatal [4, 5]. They are referred to as immune-related adverse events (irAEs). Melanoma was the most common malignancy, the majority of patients had grade 2 pneumonitis and required treatment with steroids, and all patients affected by ICI-related pneumonitis had stage IV malignancy. Potential risk factors included smoking history, prior radiotherapy, obesity, and advance stage at the time of ICI initiation.
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