PLEKHM2-ALK: A novel fusion in small-cell lung cancer and durable response to ALK inhibitors

•The first report of PLEKHM2-ALK rearrangement.•The first SCLC patient with ALK fusion with long-term benefit from ALK inhibitors.•Overall survival of more than 27 months for this case Vs 8–13 months as usual. In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) rearrangement identifies a subgroup of patients who are sensitive to ALK tyrosine kinase inhibitors (TKIs). ALK fusion is extremely rare in small-cell lung cancer (SCLC). To the best of our knowledge, only two cases of SCLC harboring ALK fusion mutation has been reported previously, both of whom carrying EML4-ALK fusion. There are no standard treatment options for SCLC patients with ALK fusion mutations. Herein, we described a rare case of ALK-rearranged SCLC responding to ALK inhibitors. Immunohistochemistry (IHC) assay and next-generation sequencing (NGS) were performed on the biopsied tumor tissue. NGS detected a novel pleckstrin homology and RUN domain containing M2 (PLEKHM2)-ALK fusion, while the IHC analysis revealed an ALK-positive tumor. For extensive SCLC patients, median OS was about 8–13 months. The patient in this case had durable clinical benefit upon the treatment with ALK inhibitors, achieving an overall survival (OS) of more than 27 months. This case provides a meaningful reference for the treatment of SCLC patients with ALK fusion mutations. This case also provides valuable information on the response to ALK inhibitors of patients with PLEKHM2-ALK fusion and better understanding of ALK-TKI applications in the future. NGS may be used as a routine test to explore more treatment opportunities for tumor SCLC patients.