High incidence and early onset of nivolumab-induced pneumonitis: four case reports and literature review

Abstract

BackgroundNivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody used as an immune checkpoint inhibitor, is commonly employed for its anti-tumor effects against various types of malignant tumors. However, its administration is complicated by immune-related adverse events (irAEs), including pneumonitis.Case presentationWe present a case series of four patients with malignant melanoma, non-small cell lung cancer, and hypopharyngeal carcinoma who demonstrated pneumonitis induced by nivolumab, and further review clinicopathological characteristics of these patients in comparison with those of previously reported patients with nivolumab-induced pneumonitis. In our series, 20% of patients who were treated with nivolumab developed pneumonitis, all of which occurred approximately 2 weeks after the initiation of nivolumab treatment. Prompt recognition of the nivolumab-induced pneumonitis allowed for successful resolution. Computed tomography scan images of the patients demonstrated predominantly cryptogenic organizing pneumonia patterns. All patients were males, who had been heavily treated with antitumor drugs prior to nivolumab.ConclusionsOur case series showed that nivolumab had a high incidence of drug-induced pneumonitis with early onset, supporting the need for renewed attention to nivolumab-induced pneumonitis, particularly in patients with a history of heavy antitumor treatments.

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

“…The authors did not employ the same terminology for the abnormality patterns, and it is thus difficult to draw comparison between the published series. Of note, organising pneumonia (figure 2b) has been the most frequent pattern observed in 19-100% of patients from the published series [76,77,79,80] and in 62.5% of the case reports [61][62][63][64][65][66][67][68][69][70][71][72].…”

“…Since 2015, >200 cases of ICI-P have been reported as isolated cases [61][62][63][64][65][66][67][68][69][70][71][72][73][74] or retrospective series involving between eight and 64 patients [75][76][77][78][79][80] (tables 2 and 3). Three series only included NSCLC patients [77][78][79], while the others involved different cancer types and, in particular, melanomas (20-95%) [75,76,80].…”

“…A CT scan was performed in the majority of ICI-P cases, with homogenous elementary radiological lesions detected in the 180 thoracic CT scans retrieved in the literature, 160 of which were described in the published series [75][76][77][78][79][80] and 20 in isolated case reports [61][62][63][64][65][66][67][68][69][70][71][72][73][74] (table 4). These were mainly ground-glass opacities (n=120, 66.7%) (figure 2a), consolidations (n=102, 56.6%) (figure 2b), reticular opacities (interlobular lines, interlobular septal thickenings) (n=47, 26.1%), bronchiectasis (n=19, 10.5%) and micronodules (n=7, 4%).…”

“…Conflicting data exist between series in terms of ICI-P severity in patients receiving monotherapy or ICI combotherapy [76,79]. By contrast, while most patients (14 out of 17) were reported as isolated cases with a grade ⩾3 ICI-P [61][62][63][64][65][66][67][68][69][70][71][72][73][74], only one death was observed [74].…”

“…In two series [79, 80], more than half of patients received broad-spectrum antibiotic therapy, without documented bacterial infection in almost all cases. Except in patients with grade 1 pneumonitis, all patients received corticosteroids, either orally or intravenously, at an initial daily dose ranging from 30 mg to 1000 mg prednisolone/prednisone equivalent [61,[64][65][66][67][68][69][70][71][72][73][74]. CT imaging resolved or remained stable in 49.6-88% and 12.8-18.8% of cases, respectively [76][77][78][79][80].…”