Long-term survival in a patient with leptomeningeal metastases from non-small cell lung cancer treated with stereotactic radiotherapy (SRT), programmed cell death protein 1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF): a case report.

Background: Leptomeningeal metastasis (LM) in non-small cell lung cancer (NSCLC) is a highly aggressive malignancy associated with poor prognosis and limited therapeutic efficacy. Currently, effective treatment options remain scarce. Although immunotherapy has revolutionised the treatment of NSCLC, its role in LM remains underexplored, and its efficacy as monotherapy is suboptimal. Preclinical and clinical studies suggest that combining programmed cell death protein 1 (PD-1) inhibitors with radiotherapy or granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance antitumor immunity. The combination therapy of stereotactic radiotherapy (SRT), PD-1 inhibitor and GM-CSF is an emerging treatment strategy currently under investigation in various advanced solid tumors, with a growing number of evidence demonstrating promising efficacy and tolerability. This case report offers novel insights and a potential therapeutic strategy for patients with NSCLC and LMs, highlighting the possibility of achieving remarkable and durable response through this combined approach. Case Description: We present the case of a 56-year-old male diagnosed with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)-negative NSCLC with concurrent brain parenchymal and LMs. After disease progression on first-line chemotherapy, he received second-line therapy consisting of SRT targeting dominant brain metastases, combined with a PD-1 inhibitor and GM-CSF. Remarkably, all lesions including the LMs, achieved complete resolution, with a progression-free survival (PFS) of 69 months to date. Conclusions: Patients with NSCLC and LMs historically face a devastating prognosis, with median survival often limited to weeks. In this case, however, the patient achieved a remarkable PFS of over 4 years following a multimodal regimen combining SRT, PD-1 inhibition, and GM-CSF. This tri-modality strategy emerges as a promising therapeutic paradigm for NSCLC-associated LM.