The biology and management of systemic anaplastic large cell lymphoma

Abstract

Systemic anaplastic large cell lymphoma (ALCL) is an aggressive CD301 non- Hodgkin lymphoma. Anaplastic lymphoma kinase positive (ALK1) ALCL is associated with the NPM-ALK t(2;5) translocation, which is highly correlated with the identification of the ALK protein by immunohistochemistry. ALK1 ALCL typically occurs in younger patients and has a more favorable prognosis with 5-year survival rates of 70% to 90% in comparison with 40% to 60% for ALK-negative (ALK2) ALCL. Studies support young age as a strong component of the favorable prognosis of ALK1 ALCL. Until recently, no recurrent translocations were identified in ALK2 ALCL. However, emerging data now highlight that ALK2 ALCL is genetically and clinically heterogeneouswith asubsethavingeither aDUSP22 translocation and a survival rate similar to ALK1 ALCL or a less common P63 translocation, the latter associated with an aggressive course. Anthracycline-based regimenssuchascyclophosphamide,doxorubicin, vincristine, and prednisone (CHOP) remain the standard first-line treatment choice for systemic ALCL, but in many patients with ALK2 ALCL, it is ineffective, and thus it is often followed by consolidative autologous stem cell transplantation. However, selection of appropriate patients for intensified therapy remains challenging, particularly in light of genetic and clinical heterogeneity in addition to the emergence of new, effective therapies. The antibody drug conjugate brentuximab vedotin is associated with a high response rate (86%) and durable remissions in relapsed/ refractory ALCL and is under investigation in the first-line setting. In the future, combining clinical and genetic biomarkers may aid in risk stratification and help guide initial patient management.