Abstract Immune checkpoint inhibitors (ICIs) have transformed the treatment of thoracic malignancies but can provoke severe immune-related adverse events such as checkpoint inhibitor pneumonitis (CIP). Grade 3-4 CIP carries mortality rates up to 15 % and typically mandates permanent ICI discontinuation. Complete recovery and sustained oncologic control after cessation remain uncommon. A 76-year-old man with pleural-dominant, poorly differentiated carcinoma (mesothelial origin not excluded) developed severe pembrolizumab-induced pneumonitis after combination carboplatin-pemetrexed-pembrolizumab therapy. He had undergone talc pleurodesis for recurrent malignant effusion. After eight cycles, he presented with progressive dyspnea and diffuse bilateral ground-glass opacities. Infectious and cardiac evaluations were negative. Grade 3 CIP was diagnosed, and pembrolizumab was permanently discontinued. High-dose intravenous methylprednisolone (1 mg/kg/day × 4 days) followed by a 4-week taper resulted in complete clinical and radiologic recovery. Maintenance pemetrexed was restarted without recurrence, and the patient maintained durable disease control with excellent functional status. This case highlights the potential for complete reversal of high-grade immune-mediated pneumonitis with early recognition and guideline-based corticosteroid therapy. Despite discontinuation of PD-1 blockade, the patient experienced sustained antitumor response, suggesting persistent immune activation beyond active treatment. Such prolonged benefit aligns with emerging evidence that once cytotoxic T-cells are effectively primed, they may continue exerting tumor surveillance independent of ongoing checkpoint inhibition. The safe reintroduction of pemetrexed monotherapy following recovery demonstrates that cytotoxic maintenance therapy can be cautiously resumed after severe CIP, providing a viable option for disease control when immunotherapy cannot be restarted. Additionally, the patient’s pleural-dominant tumor and prior talc pleurodesis may have contributed to enhanced local immune reactivity, potentially predisposing to pulmonary toxicity. This observation supports growing recognition that pleural inflammation may modify the immune microenvironment and influence the risk or course of CIP. Severe pembrolizumab-induced pneumonitis can resolve completely with prompt corticosteroid management. Durable tumor control may persist after permanent ICI discontinuation, and maintenance pemetrexed can be safely continued post-recovery. Clinicians should remain vigilant for CIP in pleural-based malignancies, particularly in patients with prior pleurodesis. This abstract is funded by: None
Salik et al. (Fri,) studied this question.
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