Abstract

The majority of patients with Hodgkin lymphoma enjoy durable remissions following front-line treatment. This typically involves combination chemotherapy with or without radiotherapy. A significant minority of patients experience relapsed/refractory disease, of whom only approximately half can be 'salvaged' with conventional second-line treatments. Until recently, for those patients either failing or who are not fit for salvage, there have been few curative alternatives. Furthermore, there is a significant risk of delayed treatment complications to conventional therapies, including secondary malignancies and cardiac disease. However, novel targeted therapies are producing excellent results in clinical trials. They provide additional treatment options for those with relapsing/refractory disease; they may have potential in front-line therapy. The anti-CD30 antibody brentuximab vedotin (BV) has been tested as monotherapy and in combination in a variety of clinical settings, including in relapsed/refractory patients and as consolidative therapy following standard second-line therapy. Nivolumab and pembrolizumab, currently used in other malignancies that are known to utilise the programmed death pathway for survival, have shown outstanding results when used as single agents in heavily pre-treated (including BV refractory) patients. Individualising and adapting a patient's treatment course, whether augmenting or rationalising therapy, based on an interim positron emission tomography/computed tomography response is an important strategy currently under exploration to minimise toxicity while maximising response. Further work is needed to explore clinical and biological factors associated with improved outcomes. Knowledge of these factors combined with the movement of novel therapies into the front-line setting will enable individualised therapy to enhance clinical responses and minimise toxicities.

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