Lowe Eric, Mossé Yael P
Children's Hospital of The King's Daughters, Norfolk, VA, USA.
Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Oncol Ther. 2024 Jun;12(2):247-255. doi: 10.1007/s40487-024-00275-6. Epub 2024 Apr 27.
Anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT) are rare cancers observed predominantly in children and young adults. ALCL accounts for 10-15% of all pediatric non-Hodgkin lymphomas and is commonly diagnosed at an advanced stage of disease. In children, 84-91% of cases of ALCL harbor an anaplastic lymphoma kinase (ALK) gene translocation. IMT is a rare mesenchymal neoplasm that also tends to occur in children and adolescents. Approximately 50-70% of IMT cases involve rearrangements in the ALK gene. A combination of chemotherapeutic drugs is typically used for children with ALK-positive ALCL, and the only known curative therapy for ALK-positive IMT is complete surgical resection. Crizotinib, a first-generation ALK inhibitor, was approved in the USA in 2021 for pediatric patients and young adults with relapsed or refractory ALK-positive ALCL; however, its safety and efficacy have not been established in older adults. In 2022, crizotinib was approved for adult and pediatric patients with unresectable, recurrent, or refractory ALK-positive IMT. This podcast provides an overview of ALK-positive ALCL and IMT. We discuss the current treatment landscape, the role of ALK tyrosine kinase inhibitors, and areas of future research.
间变性大细胞淋巴瘤(ALCL)和炎性肌成纤维细胞瘤(IMT)是罕见癌症,主要见于儿童和年轻人。ALCL占所有儿童非霍奇金淋巴瘤的10%-15%,通常在疾病晚期被诊断出来。在儿童中,84%-91%的ALCL病例存在间变性淋巴瘤激酶(ALK)基因易位。IMT是一种罕见的间叶性肿瘤,也多见于儿童和青少年。大约50%-70%的IMT病例涉及ALK基因重排。化疗药物联合通常用于ALK阳性的ALCL患儿,而ALK阳性IMT唯一已知的治愈性疗法是完整手术切除。克唑替尼是第一代ALK抑制剂,于2021年在美国被批准用于复发或难治性ALK阳性ALCL的儿科患者和年轻人;然而,其在老年人中的安全性和有效性尚未确立。2022年,克唑替尼被批准用于不可切除、复发或难治性ALK阳性IMT的成人和儿科患者。本播客概述了ALK阳性的ALCL和IMT。我们讨论了当前的治疗格局、ALK酪氨酸激酶抑制剂的作用以及未来研究领域。