Advanced Stage and Relapsed/Refractory Hodgkin Lymphoma

For those who relapse or progress after auto-HCT, a reasonable strategy therefore is to treat initially with brentuximab, unless the patient is already known to have responded poorly to brentuximab, or already has significant neuropathy. Those who achieve a CR to brentuximab are then observed. A subset of those patients will remain in remission at 5 years without further therapy. For those who relapse, or who achieve less than a CR to brentuximab, additional treatment (with brentuximab re-treatment being one option) followed by a reduced-intensity allo-HCT is a reasonable consideration. This approach has the theoretical advantages of (1) avoiding the risk of allo-HCT in the subset potentially cured by brentuximab, (2) getting patients to allo-HCT with fewer comorbidities (due to a lower total exposure to conventional chemotherapy pre-transplant), and (3) applying allo-HCT in the setting of sensitive disease/lower disease burden (due to the high efficacy of brentuximab). The results of a small study suggest that brentuximab may in fact be a very effective “bridge” to allotransplant. Chen et al¹¹³ reported on 18 patients with relapsed/refractory Hodgkin lymphoma (17 of whom had previously undergone auto-HCT) who were treated on brentuximab vedotin clinical trials. The data were retrospectively evaluated to determine the efficacy and safety of subsequent reduced-intensity allo-HCT. Remarkably, at 1 year the OS was 100%, PFS was 92%, and nonrelapse mortality was 0% with a median follow-up of 14 months. Hence, brentuximab is safe for use prior to reduced-intensity allo-HCT in heavily pre-treated patients and appears to be associated with very favorable post-transplant outcomes, particularly in comparison to older studies of allo-HCT in the era prior to brentuximab.

SUMMARY

Currently, cure is possible for the majority of patients diagnosed with advanced stage Hodgkin lymphoma. The challenge to the clinician is to provide curative treatment with the lowest risk of serious toxicities. Which regimen will best provide this balance of risk and benefit needs to be assessed based on the relapse risk, age, frailty, and comorbidity profile for an individual patient. For many patients with relapsed or refractory Hodgkin lymphoma, cure remains possible using approaches based on hematopoietic stem cell transplantation, RT, and/or brentuximab. In addition, there are now numerous conventional chemotherapy agents, RT strategies, and exciting newer agents such as PD-1 inhibitors, that can provide significant clinical benefit even when cure is not feasible.