New Strategies in Hodgkin Lymphoma: Better Risk Profiling and Novel Treatments

Abstract

Recent advances in Hodgkin lymphoma (HL) research are expected to prelude a promising new treatment era for patients and their treating physicians. Scientific investigations over the last few years have provided new insights into risk stratification, and simultaneously, a plethora of novel targeted therapies are emerging for patients with relapsed and refractory disease. These novel therapies will be tested primarily in high risk patients, since 75% of patients are cured with conventional therapies. The challenges, as HL therapy moves forward, will be using these biologic insights to identify the patients who may benefit earlier in treatment from these novel agents, and tailoring the therapy to the patient’s tumor biology. These dual aims are intertwined; as our therapeutic arsenal increases, these biologic determinants of risk may themselves inform the design of therapies and the choice of treatments for high risk patients.

Adolescent and young adult Hodgkin lymphoma: Raising the bar through collaborative science and multidisciplinary care

“…New efforts to harmonize response criteria and risk stratification are underway, which will allow direct comparison of outcomes across future trials . The recent NCI Trials Planning Consensus included a call for AYA‐specific clinical trials . Collaborations between the COG and North American cooperative research groups are in the early stages of developing common treatment protocols in select groups of AYAs with HL.…”

“…12 Differences in HL histologic subtypes have been reported across the age spectrum. 12,13 Advances in our understanding of HL biology are developing largely through retrospective analyses [16][17][18] ; there have been no prospective studies validating predictive HL biomarkers. In adults, the validated clinical index for risk stratification is the international prognostic score, however new questions about the scope of its utility in the current era are emerging.…”

“…Consensus included a call for AYA-specific clinical trials. 18,40 Predictors of overall mortality after autoHCT included a Karnofsky score <90, higher number of chemotherapeutics received prior to transplantation, and receipt of total body irradiation. 41 Targeted therapy offers to improve outcomes while reducing longterm treatment-related toxicities.…”

Fertility status of Hodgkin lymphoma patients treated with chemotherapy and adjuvant gonadotropin-releasing hormone analogues

“…Intensive therapy for advanced stages of HL such as EB is more effective; however this is accomplished at the cost of serious long term side effects including secondary leukemia, chDOR, or heart and lung damage [15]. For women of reproductive age, fertility impairment or fertility loss are important issues.…”

A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma

“…1,9,10 Several new drugs are currently in clinical development for the treatment of relapsed/refractory HL, including small molecules affecting signaling pathways and specific as well as nonspecific immunotherapeutic approaches. 11,12 Brentuximab vedotin, an antibody drug conjugate targeting CD30, was the first targeted therapy approved in 2011. Today, brentuximab vedotin is an established treatment of relapsed or refractory HL.…”