Steroid Resistant Nivolumab-Induced Pneumonitis: Game Over?

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American Journal of Respiratory and Critical Care Medicine



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Introduction: Nivolumab is an immune-checkpoint-inhibitor antibody, part of the family of IgG4 fully humanized monoclonal antibody, it targets the interaction between the programmed death 1 (PD1) and its ligand PD-L1 and PD-L2 in order to unleash the T-cell response against cancer cells. It was first approved by the U.S. Food and Drug Administration in 2014 to be used as an adjuvant therapy for melanoma, but since then its use has broadened to other types of cancer such as : Renal cell carcinoma, non-small cell lung cancer, Hodgkin Lymphoma, squamous cell carcinoma of head and neck and others. The mechanism of action is non-specific, as well as the affinity of the monoclonal antibody to cancer cells that sometimes attach to normal cells of different organ systems, causing autoimmune side effects, which are usually treated with steroids. Case: 57-year-old female patient, with history of heavy tobacco use, with diagnosis of stage IV squamous cell carcinoma of the lung type metastatic to the skull treated with combination of Carboplatin/NAB-Paclitaxel and later with Nivolumab. Patient had multiple ICU admissions due to respiratory arrest and respiratory failure secondary to Nivolumab-Induced Pneumonitis. Taper-dose steroids were unsuccessful, therefore, after disease progression, a referral to hospice was made. Discussion: Pneumonitis is a rare, but well documented, adverse effect of Nivolumab and is thought to be due to autoimmune inflammation of the lung parenchyma, the exact mechanism is still uncertain. The incidence of severe pneumonitis is highest in patients with NSCLC. It is graded from 1-4, with treatment ranging from withholding the PD-1 inhibitor and repeat imaging to permanent cessation of therapy and high dose methylprednisolone 2-4mg/kg/day tapered over 6 weeks. Clinical improvement is expected within the first 48 hours of treatment, otherwise the pneumonitis is considered steroid refractory. The timing of anti–PD-1/PD-L1–related pneumonitis onset may vary widely. Two cases were discussed by Aanika et al. The patients in both case number one and two developed pneumonitis shortly after the start of therapy; however, pneumonitis has been reported to have occurred more than a year after the first dose of immune checkpoint inhibitor therapy. A few other cases of severe steroid refractory pneumonitis have been reported in the literature. Two such cases were discussed by Andruska et al. In case number one, steroids and infliximab resulted in improvement. In the second patient, treatment with high dose steroids were ineffective contributing to patient death. However, like this case.


Diseases | Medicine and Health Sciences



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