Coexistence of a novel SETD2-ALK, EML4-ALK double-fusion in an advanced lung adenocarcinoma patient after alectinib resistant and response to immunotherapy combined with chemotherapy: a case report

The single echinoderm microtubule-associated protein-like 4 (EML4) gene and anaplastic lymphoma kinase (ALK) gene fusion is the most common variant of ALK rearrangements in non-small cell lung cancer (NSCLC). Herein, we firstly report that coexistence of a novel histone methyltransferase (SETD2)-ALK, EML4-ALK double-fusion is sensitive to alectinib as first-line therapy, and response to immunotherapy combined with chemotherapy after resistant. The patient responded to alectinib as a first-line therapy and achieved progression-free survival (PFS) for 26 months. After resistance, liquid biopsy showed that the reason of drug resistance was the disappearance of SETD2-ALK and EML4-ALK fusion variants. In addition, chemotherapy combined with immunotherapy subsequently achieved a survival benefit of more than 25 months. Therefore, alectinib may be a viable therapeutic option for NSCLC patients with double ALK fusion and immunotherapy combined with chemotherapy may be a viable therapeutic option when double ALK fusion loss may be the mechanism of alectinib resistance.