Systemic AL (λ) Amyloidosis Discovered After Neoadjuvant Pembrolizumab-Based Chemoimmunotherapy for Resectable NSCLC:...

Systemic AL amyloidosis is rarely reported in temporal association with immune checkpoint inhibitor use. We report a 69-year-old man with resectable stage IIB right upper lobe lung adenocarcinoma who received neoadjuvant pembrolizumab, carboplatin, and pemetrexed followed by robotic-assisted lobectomy. Pathology showed a 4.6-cm treated tumour bed with residual invasive adenocarcinoma (50% viable), negative margins, and no nodal metastasis (0/9). Tumour profiling demonstrated a PD-L1 tumour proportion score of 100%, a high tumour mutational burden (18 mut/Mb), microsatellite stability, and variants in BRAF, TP53 and PTPRT. In addition to the treatment effect, widespread Congo red-positive deposits were identified in lung parenchyma and multiple nodal stations. Laser microdissection with LC-MS/MS confirmed AL (λ) amyloid. Subsequent workup revealed a λ-restricted plasma cell clone (6.4%) with t (11;14), establishing systemic AL amyloidosis. He received adjuvant pembrolizumab and daratumumab-CyBorD with partial hematologic response. This case highlighted that amyloid can unexpectedly be a second diagnosis after post-neoadjuvant lung resections and that proteomic subtyping is essential for prompt haematologic staging and treatment.