Stage IV NSCLC with brain and leptomeningeal metastases responding to radiotherapy, camrelizumab, GM-CSF, and chemotherapy

What happened, in summary

This 56-year-old never-smoker was diagnosed in March 2019 with cT4N3M1c Stage IV non-small cell lung cancer, described pathologically as poorly differentiated adenocarcinoma. Disease involved the lung, a left supraclavicular lymph node, a right frontal brain metastasis, and leptomeningeal metastases. Testing showed TTF-1 and Napsin A positivity, Ki-67 60%, very high CEA, PD-L1 negative expression, no microsatellite instability, and high tumor mutational burden at 43.14 mutations/Mb. No mutations were detected in EGFR, ALK, ROS1, RET, NTRK, MET exon 14, BRAF V600E, or HER2. He first received 4 cycles of pemetrexed and cisplatin. Bevacizumab was not used because of lower-limb thrombosis and hypertension. By June 2019, lung and supraclavicular disease had progressed, a new right frontal brain metastasis appeared, cerebrospinal fluid cytology confirmed leptomeningeal metastasis, and his performance status declined to 4 with seizures and left-sided limb dysfunction. His family declined second-line chemotherapy. He then received hypofractionated radiation to the dominant right frontal brain lesion, combined with camrelizumab and GM-CSF. By September 2019, leptomeningeal metastases had completely responded, with ongoing response in brain, lung, and nodal disease. In March 2020, nab-paclitaxel was added for 2 cycles while camrelizumab and GM-CSF continued. As of March 2025, performance status had improved to 0, CEA was normal, leptomeningeal disease remained in complete response, and overall disease remained in partial response. Treatment was tolerated well overall. The main adverse event was grade 1 reactive cutaneous capillary endothelial proliferation on the face and back, with occasional grade 1 fatigue and bone pain considered related to GM-CSF. No pneumonitis, pituitary dysfunction, thyroid dysfunction, myocardial injury, or significant liver or kidney laboratory toxicity was observed. The rapid neurologic improvement helped him resume normal daily activities.