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

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OBJECTIVES 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… Click to show full abstract

OBJECTIVES 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. MATERIALS AND METHODS Immunohistochemistry (IHC) assay and next-generation sequencing (NGS) were performed on the biopsied tumor tissue. RESULTS 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. CONCLUSION 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.

Keywords: alk inhibitors; alk fusion; alk; lung cancer; fusion

Journal Title: Lung cancer
Year Published: 2019

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