Current and future immunotherapeutic approaches in Hodgkin lymphoma

Abstract

Hodgkin lymphoma (HL) has become a highly curable malignancy even in advanced stages when treated adequately. However, relapsed or refractory disease and treatment-related toxicity constitute a significant clinical challenge. Innovative approaches are thus needed to improve treatment of these mainly young patients. In HL lesions, very few malignant Hodgkin and Reed-Sternberg (HRS) cells are embedded in an immunosuppressive microenvironment of reactive cells. Novel approaches such as bispecific antibodies, antibody-drug conjugates, immune-checkpoint inhibitors or adoptive cellular therapies are currently being investigated with promising results in relapsed or refractory patients. Encouraging response rates and a favorable toxicity profile have recently been reported in early phase clinical trials with antibodies blocking the programed-death receptor 1 (PD1). This review will summarize the current clinical knowledge on mechanism, safety and efficacy of the different agents and discuss potential future strategies, which are partly already investigated within clinical trials.

The emerging role of immune checkpoint inhibition in malignant lymphoma

“…2,19 Preclinical data indicate that the PD-1/PD-L pathway contributes significantly to the immunosuppressive microenvironment of cHL. PD-1 is expressed on tumor-infiltrating and peripheral T cells in patients with cHL, 20,21 whereas PD-ligands are frequently expressed by HRS cells 22,23 and tumorinfiltrating macrophages.…”

Soluble PD‐1 and PD‐L1 as potential biomarkers for classical Hodgkin lymphoma

“…Immune checkpoint inhibition targeting programmed death-1/programmed death ligand-1 (PD-1/ PD-L1) and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) pathways reveal a new therapeutic approach focused on tumor microenvironment interactions, promoting an effective T cell mediated antitumor response. 2 Overexpression of PD-L1 on RS cells is related with downregulation of effector T cell function and represents a potent mechanism of tumor evasion. Furthermore, higher expression of PD-L1 on RS cells is associated to an advanced stage and worse prognosis.…”

Contributions of a regional approach to document hematologic disease in Mexico: a 10-year experience in an open population

“…HL affects people of all ages with peaks around 30 and after 60 years of age with this being the most common cancer in young adults [37]. The first peak in our study was at 4-7 years vs. 6-10 years in India [38].…”