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

Area of Science:

• Oncology
• Pathology
• Immunology

Background:

• Immune checkpoint inhibitors (ICIs) like pembrolizumab are used for lung adenocarcinoma.
• Systemic AL amyloidosis is infrequently associated with ICI therapy.
• Neoadjuvant therapy followed by surgery is a treatment strategy for resectable lung cancer.

Purpose of the Study:

• To report a rare case of systemic AL amyloidosis developing after neoadjuvant ICI therapy for lung adenocarcinoma.
• To emphasize the diagnostic challenges and the role of proteomic subtyping in identifying amyloidosis.
• To discuss the implications for patient management after lung cancer resection.

Main Methods:

• Case report of a 69-year-old man with lung adenocarcinoma treated with neoadjuvant pembrolizumab, carboplatin, and pemetrexed.
• Robotic-assisted lobectomy and histopathological examination of the resected lung and lymph nodes.
• Tumour profiling including PD-L1 expression, tumor mutational burden, and genetic variants.
• Laser microdissection coupled with Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for amyloid typing.
• Hematologic workup to identify the underlying plasma cell clone.

Main Results:

• The patient developed widespread Congo red-positive deposits confirmed as AL (λ) amyloid.
• Proteomic analysis identified a λ-restricted plasma cell clone with t(11;14), confirming systemic AL amyloidosis.
• Tumour profiling showed high PD-L1 expression (100%), high tumor mutational burden (18 mut/Mb), and specific gene variants.
• The patient received adjuvant pembrolizumab and daratumumab-CyBorD with a partial hematologic response.

Conclusions:

• Systemic AL amyloidosis can be an unexpected secondary diagnosis in patients undergoing treatment for lung adenocarcinoma, particularly after neoadjuvant ICI therapy.
• Proteomic subtyping is crucial for accurate diagnosis and hematologic staging of amyloidosis.
• This case underscores the need for vigilance regarding rare complications associated with novel cancer therapies.