Sequential ALK inhibitor treatment benefits patient with leptomeningeal metastasis harboring non‐EML4‐ALK rearrangements detected from cerebrospinal fluid: A case report

Thoracic Cancer

Analyn Lizaso¹  Qiongqiong Gao²  Pupu Li³  Xiangli Jiang⁴  Zhongli Zhan⁴  Qingna Yan⁴  Zhaona Li⁴  Bing Yan⁴  Chun Huang⁴ 

[1] Burning Rock Biotech Guangzhou China;Department of Respiratory Medicine Jinghai Hospital Tianjin China;Shenzhen Nanshan People's Hospital Shenzhen China;Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer Tianjin China;

关键词: Alectinib dose escalation;    ALK rearrangement;    cerebrospinal fluid;    leptomeningeal metastasis;    non‐EML4‐ALK;   

DOI  :  10.1111/1759-7714.13259

来源: DOAJ

【 摘 要 】

A 47‐year‐old female with ALK‐rearranged lung adenocarcinoma developed leptomeningeal metastasis (LM) after progression on first‐line crizotinib. Alectinib 300 mg was commenced and the patient achieved clinical and radiographic improvements. After nine months of alectinib 300 mg, she started to experience symptomatic LM. Two concurrent non‐EML4‐ALK rearrangements, LOC388942‐ALK and LINC00211‐ALK, were identified from the CSF but not from the plasma samples. With the primary lung lesions remaining stable, the alectinib dose was increased to 600 mg twice daily which alleviated the clinical symptoms of symptomatic LM. After 7.6 months of alectinib 600 mg, the patient again experienced CNS progression. With both CSF and plasma samples revealing no druggable mutations, the alectinib dose was re‐escalated to 900 mg twice daily, resulting in clinical benefits lasting for two months. Her therapy was then switched to lorlatinib which controlled the disease for 8.7 months until her demise. The LINC00211‐ALK fusion, which retains the ALK kinase domain, detected from the CSF was the mechanism of treatment efficacy in this patient. The central nervous system (CNS) has been increasingly recognized as a site of treatment failure in multiple cancers, including non‐small cell lung cancer (NSCLC). Our case demonstrated that alectinib dose‐escalation and lorlatinib overcame ALK inhibitor resistance in the CNS in an ALK‐positive LM patient. Furthermore, we provide the first clinical evidence of the efficacy of sequential ALK inhibitors in targeting LINC00211‐ALK in a patient with LM.

【 授权许可】

Unknown