Nivolumab‐related tracheobronchial chondritis: Extremely rare manifestation of an immune‐related adverse effect

Kuba, Kiyomi; Nakahira, Mitsuhiko; Inoue, Hitoshi; Kogashiwa, Yasunao; Ebihara, Yasuhiro; Sugasawa, Masashi

doi:10.1002/hed.26456

Cited by 12 publications

(5 citation statements)

References 21 publications

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“…In contrast, the management of side effects, such as radiation-induced lung injury and immune-related adverse events, has also become increasingly complicated. Few studies have reported that radiotherapy or ICIs may be implicated in the development or worsening of RP ( 12 , 13 ).…”

Section: Discussionmentioning

confidence: 99%

Lung Cancer Complicated by Relapsing Polychondritis

Arakawa¹,

Nakao²,

Sone³

et al. 2023

Intern. Med.

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A 77-year-old man presented with a 1-month history of cough, pharyngeal discomfort, and weight loss. Chest radiography revealed a mass shadow in the right upper lung field. Bronchoscopy showed multiple white nodules along the tracheal cartilage ring. Although adenocarcinoma cells were detected in the mass, several biopsy specimens of the tracheal lesions exhibited no malignancy. 18 F-fluorodeoxyglucose positron emission tomography revealed an intense accumulation in the mass, nasal septum, and tracheal cartilage. Furthermore, anti-type II collagen antibody levels were elevated. We finally diagnosed him with lung cancer complicated by relapsing polychondritis. Treatment with oral prednisolone was initiated, followed by sequential chemoradiotherapy for lung cancer.

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Section: Discussionmentioning

confidence: 99%

Lung Cancer Complicated by Relapsing Polychondritis

Arakawa¹,

Nakao²,

Sone³

et al. 2023

Intern. Med.

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“…To our knowledge, this is the first case of pembrolizumab-induced RP with isolated auricular lesions. A PubMed search for English articles describing the clinical characteristics of ICI-induced chondritis published until March 2023 yielded only five cases treated with nivolumab, another anti-PD-1 antibody ( Table 1 ) (3) , (4) , (5) , (6) , (7) . As shown in Table 1 , all patients belonging to 49-72 years age group had 50% of having hypopharyngeal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…All reported cases, excluding the present case wherein the affected cartilage was auricular, mainly included isolated tracheobronchial chondritis. Discontinuing ICIs with varied immunosuppressants improved the symptoms (3) , (5) , (6) . Notably, all previous cases were from Japan, suggesting that genetic factors could be associated with chondritis development and human leukocyte antigen (HLA).…”

Section: Discussionmentioning

confidence: 99%

Relapsing Polychondritis following PD-1 Blockade by an Immune Checkpoint Inhibitor

2023

JMA J

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Immune-related adverse events (irAEs) mimicking rheumatic diseases are observed in 1.5%-22% of patients receiving cancer therapy with immune checkpoint inhibitors (ICIs). Relapsing polychondritis (RP) is a rare autoimmune disease mainly involving auricle, nose, and airway cartilage inflammation. However, knowledge regarding RP as an irAE is scarce. Pembrolizumab, a type of ICI that regulates the programmed cell death protein-1 (PD-1), is used in patients whose cancer cannot be cured with surgery or radiation therapy. We report the first case of pembrolizumab-induced RP with isolated auricular lesions resolved without immunosuppressants. A 49-year-old man with lower lip cancer underwent surgical resection followed by reconstruction. Histopathological investigation confirmed the diagnosis of squamous cell carcinoma. Since multiple metastases 6 months post-surgery rendered the carcinoma inoperative, pembrolizumab was initiated, improving lymph node involvement. However, 4 months later, the patient developed rapidly progressive swelling and pain in both auricles. While no pathogen was detected, C-reactive protein levels were elevated (11.21 mg/dL). Computed tomography (CT) showed swelling of the bilateral auricles; the biopsy of the right auricle revealed cartilage destruction by infiltration of surrounding granulation tissue. Since these characteristic findings were not observed before pembrolizumab was initiated, we clinically diagnosed the patient with RP induced by pembrolizumab. The swelling of the auricles resolved spontaneously 1 month after pembrolizumab discontinuation. 18 F-fluorodeoxyglucose ( 18 F-FDG)-positron emission tomography/CT revealed no 18 F-FDG uptake in reduced auricular lesions. On re-administration of pembrolizumab to maintain antitumor immunity, both auricles swelled again, and pembrolizumab was switched to paclitaxel, considering the risk of tracheobronchial chondritis. Although no recurrence of auricular chondritis was observed, the patient died from cancer progression 8 months after paclitaxel administration. RP can occur as a rheumatic irAE in patients receiving anti-PD-1 therapy, and a literature review with retrospective analysis indicates that PD-1 inhibition-induced RP is unusual and atypical.

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“…ICIs for advanced cancers are known to cause immune‐related adverse events (AEs) including rheumatic diseases (1). Tracheal cartilage lesions resulting from an immune‐related AE are rare; however, tracheobronchial chondritis could be an initial manifestation of an immune‐related AE (2,3). Physicians should be aware that ICI treatment can cause tracheobronchial chondritis, which can be a fatal immune‐related AE.…”

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confidence: 99%