Novel Agents in the Treatment of Hodgkin Lymphoma: Biological Basis and Clinical Results

Hodgkin Lymphoma (HL) is a lymphoproliferative disorder of B cells that commonly has a favorable prognosis when treated with either combination chemotherapy and radiation therapy, or chemotherapy alone. However, the prognosis for patients who relapse, or have evidence for refractory disease, is poor and new treatments are needed for patients with progressive disease. HL has a unique tumor microenvironment consisting of a predominance of inflammatory cells and a minority of malignant Hodgkin and Reed-Sternberg (HRS) cells. This unique biology provides an opportunity for novel therapy approaches that either specifically target the malignant HRS cell or target the inflammatory tumor microenvironment. New therapies including antibody drug conjugates targeting CD30, small molecule inhibitors that inhibit critical cell signaling pathways, monoclonal antibodies that block immune checkpoints, or agents that modulate the immune microenvironment have all recently been tested in HL with significant clinical activity. Multiple clinical trials are currently ongoing testing these agents in the relapsed and refractory setting but also in earlier phases of therapy often in combination with more standard treatment.