Advances in targeted therapy for Hodgkin lymphoma

Introduction Based on updated estimates from the International Agency for Research on Cancer (IARC) by world region for the year ۲۰۲۲, there were close to ۸۰ hundred new cases of hodgkin lymphoma cancer, alongside ۲۲ hundred deaths from this cancer. Hodgkin's lymphoma (HL) is a rare monoclonal lymphoid neoplasm that has a critical pathogenesis characterized by a sparse population of Hodgkin and Reed-Sternberg cells surrounded by numerous dysfunctional immune cells. Despite significant improvements in prognosis for the majority of patients with Hodgkin lymphoma due to systemic chemotherapy, with or without radiation, a subset of patients remains refractory to first-line treatment or experience relapse after their initial response. The present review aims to summarize recent advances and future perspectives of targeted therapy of HL in the field. Methods The article provides a summary of the latest developments in targeted therapy for HL, analyzing data from various databases such as PubMed, Scopus, Google Scholar, and Web of Science from ۲۰۱۴ to ۲۰۲۴ and assessing their importance. Results It constitutes around one-tenth of lymphomas diagnosed in the United States and has two subtypes: classical Hodgkin’s lymphoma (cHL), which accounts for the majority of HL cases, and nodular lymphocyte predominated Hodgkin lymphoma, which represents approximately ۵% of Hodgkin lymphoma cases. Each patient's treatment relies on prognostic variables, comorbidities, and toxicity. The main treatment options for cHL are chemotherapy alone, or a “combined modality therapy”consisting of chemotherapy followed by radiation therapy. Monoclonal antibody therapy is a specific type of targeted therapy. In patients with classical HL, the malignant Reed-Sternberg cells often express a protein known as CD۳۰. Brentuximab vedotin (Adcetris®) is classified as an antibody-drug conjugate, which is an anti-CD۳۰ monoclonal antibody bound to a chemotherapeutic drug. It binds to CD۳۰-expressing cells before infiltrating cancer cells. The chemotherapeutic medicine is released after it enters the cancer cells. Fewer normal cells get injured when only cells expressing CD۳۰ are targeted. Another approach to targeted therapy is the inhibition of cancer cell-T cell signaling by checkpoint inhibitors.Blocked signals make it more probable that T lymphocytes will attack cancer cells rather than healthy ones. Nivolumab (Opdivo®) and pembrolizumab (Keytruda®) can be utilized for HL patients who have relapsed or become refractory. Nivolumab plus chemotherapy may soon be FDA-approved for pediatric and adult untreated advanced-stage HL. New approaches to targeted therapy of cHL include using Bruton's tyrosine kinase inhibitors, JAK۲ inhibitors, immunomodulatory drugs (like lenalidomide), an immunoconjugate of a monoclonal antibody to CD۲۵ with cytotoxin pyrrolobenzodiazepine (Camidanlumab tesirine), and a bispecific antibody to CD۱۶ and CD۳۰ (AFM۱۳). Recently, chimeric antigen receptor (CAR) T-cell therapy has demonstrated exceptional response rates and safety, and it is currently being studied in clinical trials for relapsed and refractory HL. Conclusion Recent advances in understanding of the biology and microenvironment of HL have led to the development of novel strategies that demonstrate significant effectiveness and tolerable toxicity, including targeted therapies, immunotherapy, and cell therapy. This review summarizes advancements in the development of innovative targeted therapeutics for HL and outlines prospective research directions in HL treatment.

کلیدواژه ها:

Cancer ، Hodgkin lymphoma (HL) ، Targeted therapies ، Immunotherapy