Importance of Multimodal Testing for Novel ALK Fusions: A Case of MTHFD1L-ALK Positive Lung Squamous Cell Carcinoma With Negative IHC.
Novel anaplastic lymphoma kinase fusion in lung squamous cell carcinoma had only 8.28-month response to anaplastic lymphoma kinase inhibitor
Importance of Multimodal Testing for Novel ALK Fusions: A Case of MTHFD1L-ALK Positive Lung Squamous Cell Carcinoma With Negative IHC.
Anaplastic lymphoma kinase (anaplastic lymphoma kinase) rearrangements are rare in lung squamous cell carcinoma (lung squamous cell carcinoma), with the clinical efficacy of anaplastic lymphoma kinase tyrosine kinase inhibitors (tyrosine kinase inhibitors) in patients harboring uncommon anaplastic lymphoma kinase fusions remaining poorly characterized.
Retrospective immunohistochemical staining of anaplastic lymphoma kinase (D5F3) was negative despite the positive genomic finding.
We report here the first identification of a novel MTHFD1L-anaplastic lymphoma kinase fusion in a 63-year-old male with a heavy smoking history diagnosed with stage IIIC lung squamous cell carcinoma.
The patient initially received induction therapy with the anaplastic lymphoma kinase tyrosine kinase inhibitors iruplinalkib, achieving a best response of stable disease (SD).
Subsequent lorlatinib provided limited benefit, with disease progression at 5.3 months following treatment self-discontinuation.
This case demonstrates limited clinical benefit from anaplastic lymphoma kinase inhibitors in lung squamous cell carcinoma with this novel fusion, expands the known mutational spectrum in non-small cell lung cancer (non-small cell lung cancer), and underscores the critical importance of confirming novel fusions at the protein expression level through multimodal testing.