Discussion
ICIs can uncommonly drive pneumonitis, with the frequency adjusted based on the number of ICIs prescribed and the primary cancer involved. Across all cancers, up to 5% of patients treated with single-agent ICI therapy may experience pneumonitis, though often the findings may simply be radiographic without symptoms. Moreover, up to 10% of patients undergoing treatment for pulmonary cancer or those with dual ICI treatment regimens experience radiographic and/or clinical pneumonitis.18 The clinical manifestations include a broad spectrum of respiratory symptoms. Given the convoluting concerns of cancer progression and infection, a biopsy is often obtained. Histopathologic findings of pneumonitis may include diffuse alveolar damage and/or interstitial lung disease, with OP being a rare variant of ILD.
Among pulmonologists, OP is felt to have polymorphous imaging findings, and biopsy is required to confirm histology; however, histopathology cannot define etiology, and consequently, OP is somewhat of an umbrella diagnosis. The condition can be cryptogenic (idiopathic) or secondary to a multitude of conditions (infection, drug toxicity, or systemic disease). It is classically described as polypoid aggregations of fibroblasts that obstruct the alveolar spaces.19 This histopathologic pattern was demonstrated in our patient’s lung biopsy. Given a prior case description of ICIs, mesothelioma, OP development, and the unremarkable infectious workup, we felt that the patient’s OP was driven by his dual ICI therapy, thereby leading to the ultimate discontinuation of his ICIs and initiation of steroids.20 Thankfully, the patient had already obtained a complete response to his ICIs, and hopefully, he can attain a durable remission with the addition of maintenance chemotherapy.
CONCLUSIONS
ICIs have revolutionized the treatment of a myriad of solid tumors and hematologic malignancies, and their use internationally is expected to increase. With the alteration in immunology pathways, clinicians in all fields will need to be familiarized with IMARs secondary to these agents, including rare subtypes. In addition, the variability in presentations relative to the patients’ treatment course was significant (between 2-9 months), and this highlights that these IMARs can occur at any time point and clinicians should be ever vigilant to spot symptoms in their patients.
It was unexpected for the 3 aforementioned rare toxicities to arise at NMVAMC among only 57 treated patients, and we speculate that these findings may have been observed for 1 of 3 reasons. First, caring for 3 patients with this collection of rare toxicities may have been due to chance. Second, though there is sparse literature studying the topic, the regional environment, including sunlight exposure and air quality, may play a role in the development of one or all of these rare toxicities. Third, rates of these toxicities may be underreported in the literature or attributed to other conditions rather than due to ICIs at other sites, and the uncommon nature of these IMARs may be overstated. Investigations evaluating rates of toxicities, including those traditionally uncommonly seen, based on regional location should be conducted before any further conclusions are drawn.