Case report of rapid lorlatinib response in lung adenocarcinoma with a novel Y chromosome intergenic ALK fusion

Rare intergenic anaplastic lymphoma kinase (ALK) fusions often elude conventional small-panel DNA next-generation sequencing, creating diagnostic blind spots. Researchers at the Second Affiliated Hospital of Hainan Medical University (Haikou, China) publish the case of a 43-year old man with stage IVB lung adenocarcinoma initially deemed driver-negative due to unrevealing small-panel sequencing and an overlooked weak immunohistochemistry signal. After rapid progression on systemic therapies, comprehensive genomic profiling of a repeat biopsy revealed a novel Y-chromosome intergenic to ALK fusion retaining the entire functional kinase domain. Lorlatinib salvage therapy yielded a profound systemic and intracranial partial response within one months. The authors conclude that this case expands the spectrum of actionable ALK fusions. Futhermore, it underscores the crucial role of comprehensive genomic profiling in uncovering cryptic fusions to enable effective precision therapy.