Lung adenocarcinoma with ALK deletion of exons 6-20 with response to sequential ALK inhibitors: a case report

Anaplastic lymphoma kinase (ALK) rearrangements are well-recognized driver oncogenes in patients with non-small cell lung cancer (NSCLC). ALK internal deletions account for only 0.01% of ALK genomic aberrations in NSCLC cases. Due to this rarity, the therapeutic efficacy of ALK inhibitors in cases harboring ALK internal deletions remains unclear. Herein, we report a case of lung adenocarcinoma harboring ALK deletions of exons 6-20 that responded to alectinib and lorlatinib treatment.

A 42-year-old woman without a history of smoking was diagnosed with stage IVB lung adenocarcinoma. Initial multiplex reverse transcription-polymerase chain reaction (mRT-PCR) (Amoy Dx Pan Lung Cancer PCR Panel) revealed no actionable mutations. Despite the high expression of programmed death ligand 1 (PD-L1) (tumor proportion score: 95%), the response to pembrolizumab and chemotherapy was limited. Comprehensive genomic profiling (CGP) (FoundationOne CDx) identified ALK internal deletions involving exons 6-20. Furthermore, subsequent immunohistochemistry (IHC) staining revealed ALK positivity. Alectinib induced a rapid partial response; disease control was maintained for nine months. After disease progression with new brain metastases, lorlatinib was initiated, resulting in a further response.

This case suggests that ALK internal deletions, even those affecting exon 20, demonstrate oncogenic potential and sensitivity to ALK inhibitors. ALK IHC remains an essential complementary test in cases of high clinical suspicion and inconclusive results using initial molecular testing.