Case Report: Four-year durable remission, cerebral oligoprogression, and femoral head necrosis following severe recurrent immune checkpoint inhibitor-related pneumonitis in a patient with stage IV lung adenocarcinoma
- 1Department of Respiratory and Critical Care Medicine, Zibo Central Hospital
- 2Department of Radiation Oncology, Zibo Central Hospital
Abstract
Severe immune checkpoint inhibitor-related pneumonitis (CIP) typically leads to the permanent discontinuation of immunotherapy; however, its long-term oncological outcomes and late drug toxicity remain poorly defined. This report describes a patient with stage IV lung adenocarcinoma who, following recurrent grade 3 CIP, achieved durable systemic remission for more than 4 years and displayed a distinctive pattern of cerebral oligoprogression. A 66-year-old male patient with stage IV lung adenocarcinoma achieved a partial response (PR) after four cycles of sintilimab combined with chemotherapy. Three weeks after the last dose, he developed grade 3 CIP complicated by acute pulmonary embolism. Recurrence occurred twice because of overly rapid corticosteroid tapering and was ultimately controlled through an ultralow tapering regimen (50 mg/day prednisone initially, reduced by 5 mg per week) combined with pirfenidone for antifibrotic therapy. Following the resolution of CIP, no further systemic antitumor therapy was administered. During 48 months of follow-up, the patient maintained complete remission (CR) of extracranial metastases; the sole site of progression was a solitary cerebellar lesion, which exhibited three episodes of oligoprogression, each of which was successfully managed with either radiotherapy or bevacizumab-based therapy. At 34 months after the onset of CIP, the patient developed bilateral osteonecrosis of the femoral head (ONFH), with right-sided slight collapse (ARCO stage III) and left-sided stage I. This case suggests a potential synergistic toxic mechanism between cumulative corticosteroid exposure (approximately 7,300 mg prednisone equivalents) and VEGF inhibition-mediated microvascular injury. This case also suggests that ultralow corticosteroid tapering combined with antifibrotic therapy can effectively manage refractory CIP; the dissociation between durable peripheral immunological memory and isolated central nervous system (CNS) progression supports the hypothesis of CNS immune privilege. Finally, clinicians must remain vigilant about long-term musculoskeletal toxicity in long-term survivors of ICI therapy.
Related
- Clinical, Radiologic, and Highest-Grade Assessment of Immune Checkpoint Inhibitor Pneumonitis in Non–Small Cell Lung Cancer
- Risk Factors for Pneumonitis in Patients with Unresectable Advanced Non-small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
- Immune Checkpoint Inhibitor-Associated Pneumonitis in Patients Treated for Metastatic Renal Cell Carcinoma.
- Influenza A (H1N1) virus infection complicated by checkpoint inhibitor pneumonitis: A case report.
- Corticosteroid-refractory checkpoint inhibitor pneumonitis in lung cancer: biological heterogeneity and mechanism-informed management
BibTeX
@article{xue2026case,
title = {{Case Report: Four-year durable remission, cerebral oligoprogression, and femoral head necrosis following severe recurrent immune checkpoint inhibitor-related pneumonitis in a patient with stage IV lung adenocarcinoma}},
author = {Yanjun Xue and Aizhen Xu and Xin Tong and Xinda Yin and Lei Wei},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1932295},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1932295/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: Four-year durable remission, cerebral oligoprogression, and femoral head necrosis following severe recurrent immune checkpoint inhibitor-related pneumonitis in a patient with stage IV lung adenocarcinoma
AU - Yanjun Xue
AU - Aizhen Xu
AU - Xin Tong
AU - Xinda Yin
AU - Lei Wei
PY - 2026
DA - 2026/10/15
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1932295
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1932295/full
AB - Severe immune checkpoint inhibitor-related pneumonitis (CIP) typically leads to the permanent discontinuation of immunotherapy; however, its long-term oncological outcomes and late drug toxicity remain poorly defined. This report describes a patient with stage IV lung adenocarcinoma who, following recurrent grade 3 CIP, achieved durable systemic remission for more than 4 years and displayed a distinctive pattern of cerebral oligoprogression. A 66-year-old male patient with stage IV lung adenocarcinoma achieved a partial response (PR) after four cycles of sintilimab combined with chemotherapy. Three weeks after the last dose, he developed grade 3 CIP complicated by acute pulmonary embolism. Recurrence occurred twice because of overly rapid corticosteroid tapering and was ultimately controlled through an ultralow tapering regimen (50 mg/day prednisone initially, reduced by 5 mg per week) combined with pirfenidone for antifibrotic therapy. Following the resolution of CIP, no further systemic antitumor therapy was administered. During 48 months of follow-up, the patient maintained complete remission (CR) of extracranial metastases; the sole site of progression was a solitary cerebellar lesion, which exhibited three episodes of oligoprogression, each of which was successfully managed with either radiotherapy or bevacizumab-based therapy. At 34 months after the onset of CIP, the patient developed bilateral osteonecrosis of the femoral head (ONFH), with right-sided slight collapse (ARCO stage III) and left-sided stage I. This case suggests a potential synergistic toxic mechanism between cumulative corticosteroid exposure (approximately 7,300 mg prednisone equivalents) and VEGF inhibition-mediated microvascular injury. This case also suggests that ultralow corticosteroid tapering combined with antifibrotic therapy can effectively manage refractory CIP; the dissociation between durable peripheral immunological memory and isolated central nervous system (CNS) progression supports the hypothesis of CNS immune privilege. Finally, clinicians must remain vigilant about long-term musculoskeletal toxicity in long-term survivors of ICI therapy.
SN - 1663-9812
ER -