Ensartinib in a primary pulmonary ALK-rearranged mesenchymal neoplasm harboring a novel HMBOX1::ALK fusion: a case report and literature review

Qi Liang¹Xingyu Jiang¹Ziwei Zhou¹Yali Jiang²Siqi Ni¹Tingyu Zhao¹Xiao Zhang¹Huanhuan Xu³Qi-Xing Gong¹Lingxiang Liu^1*

• ¹First Affiliated Hospital, Nanjing Medical University, Nanjing, China
• ²The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Yining, Xinjiang, China
• ³Jiangsu Province Geriatric Hospital, Nanjing, Jiangsu Province, China

Anaplastic lymphoma kinase (ALK) gene rearrangements have been increasingly detected in mesenchymal neoplasms. ALK-rearranged mesenchymal neoplasms occur mainly in superficial tissues but rarely in internal organs. Herein, we firstly report a primary lung lesion presenting as a rare ALK-rearranged mesenchymal neoplasm. The patient diagnosed with primary pulmonary ALK-rearranged mesenchymal neoplasm (PPAMN) received ensartinib as postoperative adjuvant therapy, achieving a diseasefree survival of 10 months. Continuation of ensartinib as first-line treatment enabled him to benefit from a partial response, with a progression-free survival of 11 months.Second next-generation sequencing (NGS) revealed elevated HMBOX1::ALK abundance along with secondary NF2 mutation. After local radiotherapy combined with ensartinib continuation, his disease was temporarily stable for 7 months. Unfortunately, this disease became uncontrolled with an overall survival (OS) of 34 months. This is the first case of ALK-rearranged mesenchymal neoplasm manifested as a primary lung lesion and a novel HMBOX1::ALK fusion was identified by NGS. The family of ALKrearranged mesenchymal neoplasms is expanding and ensartinib could be a potential treatment option for patients with HMBOX1::ALK. Repeated biopsy and NGS detection are critical to guide treatment selection at disease progression.