Immune checkpoint inhibitors do not exacerbate asthma in patients with cancer
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Patients with cancer undergoing treatment with immune checkpoint inhibitors did not experience exacerbations in their asthma, according to a study published in Annals of Allergy, Asthma & Immunology.
“Immune checkpoint inhibitors commonly cause allergic skin reactions,” Donald Y.M. Leung, MD, PhD, division head of pediatric allergy and clinical immunology at National Jewish Health, Denver, told Healio.
“Since asthma is a common problem and commonly causes hospitalization and emergency room visits, we wanted to know whether immune checkpoint inhibitors had an effect on asthma,” Leung said.
The role of immune checkpoint inhibitors (ICIs) in cancer treatment is increasing, according to the researchers. These agents block the natural regulation of T cells, activate cytotoxic T cells and prompt the immune system to begin activity against tumors. However, adverse events have occurred with this treatment.
According to the researchers, there may be a link between immune-related adverse events and an autoimmune process secondary to T-cell receptor inhibitory phosphatases that remain tolerant to autoantigens.
Noting an increase in T helper 2 cell lymphocytes and eosinophils in patients with asthma, the researchers investigated whether ICIs make underlying asthma worse.
The study enrolled 83 patients with immune-related cutaneous adverse events of grade 2 or higher at Memorial Sloan Kettering Cancer Center in New York and National Jewish Health, as well as 32 patients receiving ICIs without any immune-related cutaneous adverse events.
A questionnaire on atopic diseases revealed that 13 patients (average age, 65 years; range, 41-87; men, n = 9; white, n = 11) had a history of asthma, with six of them reporting pruritis without rash, three with eczema, one with a maculopapular rash and three with no cutaneous adverse events.
Four of these patients were not receiving any asthma medications, whereas four had inhaled corticosteroids (ICS) with short-acting bronchodilators as rescue. Two had ICS with a long-acting bronchodilator with a short-acting beta agonist (SABA) as rescue.
Also, one of these patients only had SABA, one only had an oral leukotriene inhibitor and one had both.
Once these 13 patients began receiving an ICI, clinicians added 5 mg of prednisone to one patient’s asthma regimen, which had included ICS, SABA and a leukotriene inhibitor. They also added a leukotriene inhibitor to a regimen of ICS, SABA and montelukast for a second patient.
The other 11 patients did not have any change in their asthma treatment once ICI administration began, although nine of them saw their eosinophil levels increase.
ICI use may induce adverse events in the lungs such as pneumonitis, according to the researchers, but there was no evidence of asthma exacerbations in this patient population.
“Immune checkpoint inhibitors did not have any influence on the occurrence of respiratory allergy,” Leung said, adding that these findings should provide “reassurance that this commonly used cancer drug is safe for asthmatics.”
Next, Leung said, the researchers hope to characterize the mechanism by which ICIs trigger skin reactions.
For more information:
Donald Y.M. Leung, MD, PhD, can be reached at leungd@njhealth.org.
Perspective
Back to TopUnderstanding the spectrum of immune-related adverse events in patients treated with checkpoint inhibitors is important. These observations, gleaned from a cohort of patients with skin immune-related adverse events who were retrospectively evaluated for asthma in this study, accord with experience treating tens of thousands of patients across many clinical trials and in clinical practice. A diagnosis of asthma is rarely a concern in patients commencing ICIs for cancer. Prospective studies focused on understanding severe immune-related adverse events — those that lead to stopping ICIs or rarely to death, and/or those that affect patient quality of life — are important.
Perspective
Back to TopDihua Yu, MD, PhD, and Yi Xiao, PhD
ICIs have become a core pillar of therapy for many types of cancer. However, they also bring a unique class of toxicities termed immune-related adverse events that can affect multiple organ systems through poorly understood mechanisms.
ICI-related pneumonitis (ICI-P) is a potentially fatal immune-related adverse event. The incidence of ICI-P reported in clinical trials was about 3% to 5%, yet some studies have suggested that the real‐world incidence may be significantly higher. Importantly, ICI-P was the most common reason for deaths among immune-related adverse events, according to several studies.
However, the risk factors for ICI-P are still unclear. Although some suspected factors such as sex, smoking history and baseline lung disease showed correlation with occurrence of ICI-P, more evidence is needed to further confirm these findings.
A group led by Donald Y.M. Leung, MD, PhD, explored if ICI-P is associated with pre-existing asthma in patients. They found that among 13 patients who reported a history of asthma and received treatment with ICIs, only two patients experienced asthma exacerbation. The 11 remaining patients had no asthma exacerbation event although most of them, nine out of 11, had an increase in eosinophil levels. Therefore, it is unlikely that ICIs worsen underlying asthma or induce exacerbation of asthma.
This finding contradicts with previous studies that have suggested that a prior diagnosis of asthma is associated with an increased risk for ICI-P. But it is worth noting that patients with lung cancer were not included in this study, whereas previous studies included patients with lung cancer.
Given that patients with non‐small cell lung cancer (NSCLC) had higher incidence of ICI-P compared with patients with other cancer types, study of another larger patient cohort including patients with NSCLC is necessary to validate this finding.
Additionally, the increased eosinophils in most of the patients with a history of asthma should be cautious. A recent study showed that a high level of peripheral eosinophil count was associated with an increasing risk for ICI-P in NSCLC patients, which is potentially life‐threatening if not treated timely and correctly.
Clinicians need to pay more attention to ICI-P. Identifying factors that increase the risk for ICI-P is an urgent clinical challenge.
Dihua Yu, MD, PhD
Professor, Biologist and Hubert L. & Olive Stringer Distinguished Chair in Basic Science
Department of Molecular and Cellular Oncology
University of Texas MD Anderson Cancer Center
Yi Xiao, PhD
Assistant Professor, Department of Molecular and Cellular Oncology
University of Texas MD Anderson Cancer Center
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