Stage IV squamous NSCLC: durable pembrolizumab response followed by invasive aspergillosis, marrow failure, and death

What happened, in summary

This 58-year-old man presented in March 2023 with newly diagnosed left-sided squamous non-small cell lung cancer. CT showed a left perihilar soft-tissue mass involving the left upper lobe and lingula, with mediastinal and bilateral hilar lymphadenopathy and multiple small nodules in both lungs. A left adrenal lesion was seen, but metastatic involvement could not be confirmed. Overall staging was cT4N3M1, Stage IV. The tumor had PD-L1 expression of 20% and no actionable driver alterations. He was not a candidate for surgery or radiation, so treatment began with pembrolizumab, paclitaxel, and cisplatin for 6 cycles, followed by pembrolizumab maintenance for 18 cycles. After 3 cycles, CT showed marked shrinkage of the primary tumor and involved lymph nodes, a partial response that remained stable through September 2024. In October 2024, about 1 month after his last pembrolizumab dose, he developed fever and left chest pain. CT showed a new cavitary left lower-lobe consolidation, and sputum culture grew Klebsiella pneumoniae. Despite antibacterial treatment, imaging progressed. In December 2024, he was readmitted with cough, sputum, and hemoptysis. Blood mNGS detected Aspergillus niger, and imaging suggested angioinvasive infection; he received liposomal amphotericin B, then isavuconazole. Infection improved radiologically, but the left hilar tumor progressed and he developed severe pancytopenia. Bone marrow biopsy showed an aplastic-anemia-like marrow failure pattern. Despite transfusions, hemostatic therapy, corticosteroids, and supportive care, cytopenias persisted. He declined further treatment, requested discharge, and died at home a few days later. His case balances two realities: the lung cancer responded for a long period to immunotherapy, but later infection and immune-related marrow failure became fatal.