Clinical characteristics and management of immune checkpoint inhibitor‐related pneumonitis: A single‐institution retrospective study

Abstract

Introduction The increasing application of immune checkpoint inhibitors (ICIs) will cause more checkpoint inhibitor‐related pneumonitis (CIP), which is a common cause of ICI‐related death. The clinical management of CIP needs further optimization. Methods Patients who were managed at Peking Union Medical College Hospital (PUMCH) between February 2017 and December 2019 with a diagnosis of CIP were retrospectively analyzed. Clinical data including clinical manifestations, radiologic data, laboratory and bronchoscopy results, treatments, and outcomes were collected and analyzed. The Mann–Whitney test was used to compare patients with and without co‐infections. Results In total, 48 CIP cases in 42 patients were analyzed. The median time from the first dose of ICI to the onset of CIP was 1.9 months (range: 0.1–13.7). Grade 3–4 (G3–4) accounted for 30 cases (71.4%). The most common symptoms were cough (88.1%) and dyspnea (78.6%). The median starting dose of equivalent prednisone (EP) was 55 mg (range: 30–200) for all patients. The median total duration of glucocorticosteroids (GCS) treatment was 42.5 days (range: 15−89). Three patients (7.14%) died because of infection. A higher starting dose and longer duration of GCS (≥30 mg/day; p = 0.001) were associated with opportunistic infection. Chest computed tomography (CT) showed diverse and asymmetrical lesions. Twelve patients were re‐challenged, and six patients developed recurrent CIP. Conclusions The clinical and imaging manifestations of CIP are various, and differential diagnosis of exclusion is essential. GCS at 1–2 mg/kg is feasible to treat CIP, but the duration of GCS ≥30 mg/day should be used with caution, given the high risk of acquired infections. Re‐challenges of ICI are feasible, but the recurrence of CIP needs to be closely monitored.

Safety of Immune Checkpoint Inhibitor Resumption after Interruption for Immune-Related Adverse Events, a Narrative Review

“…Studies having specifically assessed the safety of ICI retreatment after ICI discontinuation for irAEs remain scarce and heterogenous. Most are based on small samples of patients [ 18 , 19 , 20 ] or focused only on the recurrence rate of the same irAE after an ICI rechallenge [ 21 ]. Moreover, patients with grade ≥3 irAEs have been excluded from many of these studies [ 22 , 23 , 24 , 25 ].…”

Pulmonary Toxicities Associated With the Use of Immune Checkpoint Inhibitors: An Update From the Immuno-Oncology Subgroup of the Neutropenia, Infection & Myelosuppression Study Group of the Multinational Association for Supportive Care in Cancer

“…The onset of ICI-Pneumonitis is most often heralded by symptoms of dyspnea (53-79%), dry cough (35-88%), low-grade fever (12%), and chest pain (7%). The time from the administration of the first dose of an ICI to the occurrence of ICI-Pneumonitis varies widely from 1.9 to 24 months, with a median time of 2.8 months (Hassel et al, 2017;Wang et al, 2021). Earlier occurrences have been reported with combination therapies (median 2.7 vs. 4.6 months) and among patients with lung cancer (2.1 months) compared to melanoma (5.1 months) (Zhu et al, 2020).…”

“…Histologic descriptions of ICI-Pneumonitis range from NSIP, OP, granulomatous inflammation, and cellular interstitial pneumonitis. Less commonly, acute fibrinous OP and diffuse alveolar damage are reported (Naidoo et al, 2017;Wang et al, 2021). Associated inflammatory infiltrates are typically lymphocyte-predominant.…”

“…Poorly formed granulomas and increased numbers of eosinophils may also be seen (Naidoo et al, 2017;Hattori et al, 2019;Jodai et al, 2019). Increased levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and to a lesser extent, interleukin-8 (IL-8) and interleukin-10 (IL-10) represent nonspecific signals of inflammation, but cannot distinguish inflammation in the setting of infection from a drug-related inflammatory response (Larsen et al, 2019;Wang et al, 2021). Differential expression of IL-17 in BAL IFNγ + IL-17 -CD8 + T and CXCR3 + CCR6 + Th17/ Th1 cells was noted in BAL fluid of patients with ICI-Pneumonitis compared to patients with pneumonia; however, larger studies are needed to confirm these findings (Kim et al, 2021).…”

“…Reported mortality rates associated with grade 3-4 ICI-Pneumonitis are high (22-33%), highlighting the need for early detection and optimization of treatment (Wang et al, 2018;Tone et al, 2019). Opportunistic infections triggered by prolonged high-dose steroid therapy are thought to be an important cause of ICI-Pneumonitis-related major morbidity and potentially mortal (Wang et al, 2021)). Patients that show no signs of clinical or radiographic improvement after 48 h of steroid therapy are deemed to be steroid-refractory.…”