Abstract Introduction Pembrolizumab is a PD-1 inhibitor approved for advanced non-small cell lung cancer (NSCLC) but is well-documented to cause immune-mediated pneumonitis as an adverse event, with higher incidence in NSCLC compared to other malignancies. 1 The risk is significantly increased in patients with pre-existing interstitial lung disease (ILD) or pulmonary fibrosis. 2, 3 Immune checkpoint inhibitor (ICI) pneumonitis in this setting may present as acute exacerbation or organizing pneumonia and may not fully resolve despite immunosuppression, often resulting in progressive fibrosis. 3, 4 Guidelines recommend permanent discontinuation of ICI therapy and aggressive immunosuppression for severe or steroid-refractory cases. Case Presentation A 75-year-old man with stage IV lung adenocarcinoma on pembrolizumab and pemetrexed, with underlying COPD, obstructive sleep apnea, and interstitial lung disease, presented with worsening dyspnea, hypoxia, and increased oxygen requirements (baseline 4 L/min). Imaging revealed progressive bilateral ground-glass opacities superimposed on chronic fibrotic lung disease, without pulmonary embolism. Broad infectious workup including PJP, AFB, Legionella, and viral panels was largely negative except for HSV-1 in bronchoalveolar lavage. He was treated empirically for pneumonia and initiated on pulse-dose methylprednisolone (1000 mg/day for 3 days). Despite treatment with high-dose steroids, his oxygen requirements continued to rise, and chest imaging showed worsening infiltrates, consistent with steroid-refractory ICI pneumonitis. Given the lack of improvement, IVIG was administered over two days (2 g/kg total), as his steroids were slowly tapered. Within days, the patient demonstrated marked improvement in oxygenation and radiographic resolution of infiltrates. He was successfully weaned to his baseline oxygen requirements, transitioned to oral steroids with a prolonged taper, and discharged home in stable condition. Discussion ICI-induced pneumonitis occurs in approximately 3-5% of patients receiving PD-1 inhibitors, but severity and outcomes vary widely. Pre-existing ILD increases the risk of both developing and worsening pneumonitis, often resulting in more severe and treatment-resistant cases. Corticosteroids remain the mainstay, yet up to 20% of patients may not respond adequately. In such cases, alternative immunosuppressive or immunomodulatory therapies—such as infliximab, mycophenolate, or IVIG may be required. IVIG exerts immunomodulatory effects by neutralizing pathogenic antibodies and downregulating inflammatory cytokines. Although data are limited, this case demonstrates that IVIG can be effective in severe, steroid-refractory ICI pneumonitis, even in patients with coexisting fibrotic ILD. Early recognition of steroid resistance and timely initiation of adjunctive therapy may improve outcomes and avoid irreversible lung injury. Further studies are needed to define optimal escalation strategies in steroid-refractory immune-related pneumonitis. This abstract is funded by: None
Reddy et al. (Fri,) studied this question.
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