Minimising the Toxicities of First Line Hodgkin Lymphoma Treatment in the Modern Era

SIMPLE SUMMARY: Due to advances in chemotherapy and radiotherapy over recent decades, Hodgkin lymphoma is now a curable disease in the vast majority of younger patients. While treatment has become very effective, patients are burdened with significant short- and long-term side effects such as infections, infertility, organ failure and secondary malignancies. In this article we review the strategies that have been used to reduce the toxicity of treatment while maintaining high cure rates, and how the current treatment of Hodgkin lymphoma has evolved based on the success of these strategies. ABSTRACT: Striking advances in the treatment of Hodgkin lymphoma over the last 30 years have culminated in high rates of disease-free survival in younger patients with early and advanced stage disease. In this review we focus on strategies that have evolved over recent years to reduce short and long-term toxicities of treatment. These strategies include the selection of first-line chemotherapy, the stratification of patients based on initial response and subsequent adaptation of treatment, the addition of novel agents (e.g., brentuximab vedotin), the removal of specific drugs (e.g., bleomycin), the use of drug substitution, and the removal of consolidation radiotherapy based on interim and end of treatment PET assessment. While these strategies have successfully reduced toxicity of Hodgkin lymphoma therapy, the cornerstone of treatment continues to be combination chemotherapy and radiotherapy with significant short- and long-term side effects. To further reduce toxicity while maintaining or improving efficacy, we shall need to incorporate novel agents into our first-line treatment algorithms, and several such potentially practice-changing trials are underway.