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Recent advancements have significantly transformed the treatment landscape for relapsed or refractory classic Hodgkin lymphoma. The emergence of innovative therapies promises better outcomes and sets the path for personalized treatment strategies.

  • Classic Hodgkin lymphoma cure rates have improved with chemotherapy, yet 10–30% of patients experience relapse or refractory disease.
  • The last decade has witnessed the approval of three impactful novel agents: brentuximab vedotin, nivolumab, and pembrolizumab.
  • Current research highlights a tailored approach to treatment, emphasizing the role of novel agents in both pre-transplant salvage therapy and post-transplant maintenance.

Frontline combination chemotherapy for classic Hodgkin lymphoma (cHL) typically produces positive outcomes. However, relapses or instances of primary refractory disease still pose significant challenges, with rates ranging between 10–30% depending on the disease stage and other risk factors. The introduction of biologically targeted agents like brentuximab vedotin and programmed death-1 (PD-1) inhibitors in the past decade has brought in a new era in the treatment of cHL, resulting in improved survival rates, according to a study published in the journal Cancers.

Modern Management for Transplant-Eligible Patients

For younger patients who are in good health and have relapsed or refractory (R/R) cHL, the present standard of care protocol is salvage chemotherapy followed by autologous hematopoietic cell transplantation (AHCT). Key factors affecting post-AHCT outcomes include the nature of the disease (primary refractory or early relapse) and pre-transplant remission status based on PET evaluations. Recent studies have found that incorporating novel agents like brentuximab vedotin and PD-1 inhibitors into pre-transplant salvage therapy and post-transplant maintenance results in better outcomes.

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Considering Transplant-Ineligible Patients

For patients ineligible for AHCT, novel agents have made a significant impact. With a focus on factors such as age, disease characteristics, and first-line treatments, clinicians now have a broader range of therapeutic options to choose from. Especially promising are the PD-1 inhibitors pembrolizumab and nivolumab, which are effective and have led to improved health-related quality of life for R/R cHL patients.

Innovative Immunotherapy Interventions on the Horizon

The immune evasion tactics of cHL present numerous challenges. However, as our understanding of the disease deepens, researchers are exploring combinations of PD-1 inhibitors with other agents that activate the immune response. In addition, there’s growing excitement around novel therapies like antibody–drug conjugates, bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapy, all of which show potential for further reshaping the treatment landscape of cHL.

Concluding Thoughts for Clinicians

The rapid advancements in cHL treatment have opened new avenues for healthcare providers. With an expanding arsenal of therapeutic options, clinicians can now provide a more tailored approach to treating R/R cHL patients. These novel treatments may not only improve outcomes but also fit the needs of individual patients with specific profiles. As research continues, the field can expect more refined strategies, which may help clinicians develop even more effective treatment strategies for their patients with cHL.


Randall, M. P., & Spinner, M. A. (2023). Optimizing treatment for Relapsed/Refractory classic Hodgkin lymphoma in the era of immunotherapy. Cancers, 15(18), 4509. https://doi.org/10.3390/cancers15184509