Stage IV PD-L1-high lung adenocarcinoma: remission on chemotherapy after tislelizumab-associated KLHL11-IgG cerebellitis

What happened, in summary

This 53-year-old man was diagnosed with Stage IV lung adenocarcinoma, T3N2M1a. His history included active smoking, prior pulmonary tuberculosis, and coronary artery disease with a coronary stent placed in 2018. Pathology showed TTF-1-positive adenocarcinoma. PD-L1 expression was high, with 70% of tumor cells positive, while ALK, ROS1, and EGFR were all wild type. He started tislelizumab every 3 weeks with cisplatin and pemetrexed. After 3 cycles, CT showed a partial response with shrinkage of the primary lung tumor. After the fourth cycle, he developed fever, fatigue, headache, anorexia, and vomiting, but imaging did not show brain metastasis or abdominal disease. Two weeks after the sixth tislelizumab cycle, he developed slurred speech, dizziness, gait instability, recurrent vomiting, falls, and severe ataxia. MRI showed inflammatory lesions in the right cerebellar hemisphere. Repeated lumbar punctures did not show infection or cancer spread. Serum and CSF testing were positive for KLHL11-IgG, leading to a diagnosis of immune-checkpoint-inhibitor-related KLHL11-IgG cerebellitis. Tislelizumab was stopped, while cisplatin and pemetrexed continued to maintain cancer control. High-dose IV methylprednisolone plus IVIG gave only partial neurologic improvement. Efgartigimod was added weekly for 4 weeks, and walking and dizziness improved rapidly. At 6 months, he had only occasional dizziness and mild slurred speech. At 1 year, serum KLHL11-IgG was negative, MRI showed complete resolution of cerebellar inflammation, and the lung cancer remained in remission on cisplatin plus pemetrexed. The neurologic recovery is clinically important because severe ataxia initially left him unable to walk independently, yet rescue therapy allowed major functional improvement while cancer therapy continued.