Abstract
Treatment for Hodgkin lymphoma (HL) has evolved considerably from the time it was originally described in the 19th century with many patients now being cured with frontline therapy. Despite these advances, upwards of 10% of patients experience progressive disease after initial therapy with an even higher percentage relapsing. Until recently there had been limited therapeutic options for relapsed and/or refractory HL outside of highly intensive chemotherapy with stem cell rescue. Improved understanding of the pathophysiology of HL, coupled with the emergence of more targeted therapeutics, has reshaped how we view the treatment of relapsed/refractory HL and its prognosis. With this, there has been an increased focus on immunotherapies that can reprogram the immune system to better overcome the immunosuppressive milieu found in HL for improved cancer cell killing. In particular, chimeric antigen receptor (CAR) T cells are emerging as a valuable therapeutic tool in this area. Building on the success of antibody-drug conjugates directed against CD30, CAR T cells engineered to recognize the same antigen are now reaching patients. Though still in its infancy, CAR T therapy for relapsed/refractory HL has shown exceptional promise in early-stage clinical trials with the potential for durable responses even in patients who had progressed through multiple lines of prior therapy. Here we will review currently available data on the use of CAR T cells in HL, strategies to optimize their effectiveness, and how this therapy may fit into the treatment paradigm of HL going forward.
Highlights
Hodgkin lymphoma (HL) is a B cell malignancy that affects ~8000 people yearly of all ages with the highest incidence in young adults
Salvage options for treatment in these cases have generally focused on high-dose chemotherapy followed by autologous stem cell transplantation (ASCT), which remains the standard of care to date
Low levels of cytokine release syndrome (CRS) seen in this study and subsequent trials are in contrast to what has been seen to date with other chimeric antigen receptor (CAR) T cell-based approaches, anti-CD19 based CAR therapies
Summary
Hodgkin lymphoma (HL) is a B cell malignancy that affects ~8000 people yearly of all ages with the highest incidence in young adults. The emergence of more targeted therapeutics, including anti-CD30 antibody-drug conjugates and immunotherapy, has reshaped how we approach treatment for relapsed/refractory disease [4,5] Even with these advances there remain a significant fraction of patients who progress, leading to more than 1000 deaths yearly from HL. CAR T cells have shown exceptional promise in trials for non-Hodgkin lymphoma with even heavily pretreated patients showing high response rates with the potential for durable responses [8]. Given their success in other lymphomas and hematologic malignancies, studies are evaluating how to improve their efficacy in relapsed/refractory (r/r) HL [9]. Though the use of CAR T cells for the treatment of HL had lagged behind initially, recent trials show that this is an effective approach for the treatment of relapsed or refractory disease
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