Personalized Medicine in Hodgkin Lymphoma?

Abstract

Hodgkin lymphoma (HL) patients are usually being allocated to early favorable, early unfavorable, and advanced-stage risk groups. Intensity of treatment thus depends on clinical stage and the presence of clinically defined risk factors. With current standard treatment approaches including chemo- and/or radiotherapy, cure rates range from 60 to 90%. With this excellent prognosis, many patients would be sufficiently treated with less aggressive strategies than the current standard. To avoid overtreatment in low-risk patients and maintain the appropriate treatment intensity for high-risk patients at the same time, response-adapted treatment stratification based on interim positron emission tomography (PET) is under investigation. Treatment stratification on the basis of the mutation status of specific genes or upon guidance by minimal residual disease (MRD) as currently evaluated in other malignancies would be even more desirable but is difficult in HL. The reason for this is that the malignant Hodgkin and Reed−Sternberg (H-RS) cells usually account for less than 1% of cells in the lymphoma tumor tissue at initial diagnosis. However, several signaling pathways dysregulated in H-RS cells were identified recently and an increasing number of drugs specifically targeting these pathways are becoming available. Small molecules, monoclonal antibodies, and immunotoxins are among the most promising candidates for a more selective treatment and might become part of future personalized treatment approaches in HL patients. This chapter gives an overview on current and possible future targeted approaches in HL.