Genetic lesions and targeted therapy in Hodgkin lymphoma

Ther Adv Hematol. 2023 Jan 12:14:20406207221149245. doi: 10.1177/20406207221149245. eCollection 2023.

Abstract

Hodgkin lymphoma is a special type of lymphoma in which tumor cells frequently undergo multiple genetic lesions that are associated with accompanying pathway abnormalities. These pathway abnormalities are dominated by active signaling pathways, such as the JAK-STAT (Janus kinase-signal transducer and activator of transcription) pathway and the NFκB (nuclear factor kappa-B) pathway, which usually result in hyperactive survival signaling. Targeted therapies often play an important role in hematologic malignancies, such as CAR-T therapy (chimeric antigen receptor T-cell immunotherapy) targeting CD19 and CD22 in diffuse large B-cell lymphoma, while in Hodgkin lymphoma, the main targets of targeted therapies are CD30 molecules and PD1 molecules. Drugs targeting other molecules are also under investigation. This review summarizes the actionable genetic lesions, current treatment options, clinical trials for Hodgkin lymphoma and the potential value of those genetic lesions in clinical applications.

Keywords: CAR-T therapy; Hodgkin lymphoma; JAK-STAT; NFκB; immune evasion; immunotherapy; molecular mechanisms; primary immunodeficiency; targeted therapies.

Publication types

  • Review