Anti-EML4-ALK Monoclonal Antibody, clone XH047

Rationale: The anaplastic lymphoma kinase (ALK) fusion has been identified to be a driver gene in lung cancer, and serves as important diagnostic and therapeutic targets. Owing to the advanced sequencing technologies, new partner genes of ALK have been constantly detected. Patient concerns: A 55-year-old Chinese woman went to our hospital because of cough and expectoration for 1 year. The patient had no fever, chest pain and hemoptysis. Diagnoses: She was diagnosed with lung adenocarcinoma. Because she had no operational condition, combination chemotherapy with docetaxel and cisplatin (CP) for 4 cycles was adopted. However, computed tomography (CT) scan indicated progression disease (PD). To explore possibility of targeted therapy, the tumor samples were subjected to next-generation sequencing (NGS), and a rare double ALK fusion variant EML4-ALK and CDK15-ALK was identified. Interventions and outcomes: The patient subsequently received crizotinib treatment, and achieved partial response (PR). No significant drug related adverse reactions were found during crizotinib treatment. The progression-free survival achieved 23 months. Lessons: Together, we identified a rare double ALK fusion variant, EML4-ALK and CDK15-ALK, in a patient with lung adenocarcinoma. The patient benefited from crizotinib treatment, which could provide a certain reference for the patients with such gene alteration.

Rationale:The anaplastic lymphoma kinase (ALK) rearrangements represent a subtype of nonsmall-cell lung cancer (NSCLC), and targeting ALK has radically changed the treatment of NSCLC. Crizotinib, as an ALK inhibitor, has been used in the treatment of ALK-rearranged NSCLC for several years and some adverse effects should be given attention.Patient concerns:A 64-year-old woman with a no-smoking history visited hospital in November 2016 because of a persistent cough, expectoration, and progressive dysphagia for 2 months.Diagnoses and interventions:She was diagnosed with primary lung adenocarcinoma, accompanied by pleural and bone metastases. After receiving chemotherapy for nearly 1 year, she showed progressive disease. DNA-sequencing identified an intergenic ALK rearrangement. Surprisingly, RNA-sequencing revealed the EML4-ALK fusion transcript. Subsequently, this patient switched to crizotinib therapy.Outcomes:The patient achieved partial response after 1-month treatment. However, this patient suffered a severe sinus bradycardia after 4 months of treatment. When reducing the dose of crizotinib, the side effect was alleviated and this patient showed stable disease until now.Lessons:Given that the severe sinus bradycardia was an unusual adverse effect, physicians should be aware of these side effects when using crizotinib. Moreover, it should be noted that this patient harbored an intergenic ALK rearrangement identified by DNA-sequencing, but EML4-ALK fusion transcript verified by RNA-sequencing. However, the mechanism remains unknown and requires further research.