Optimal Treatment for Advanced-Stage Disease

The treatment of advanced-stage disease has been debated for the past decade, primarily focused on ABVD and the German-derived regimen, escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). ABVD became the standard of treatment following trials that showed ABVD was as or more effective than the regimen of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), and had fewer toxicities. More recently, the German Hodgkin Lymphoma Study Group (GHSG) has advocated BEACOPP as the new standard of treatment for patients with high-risk, advanced-stage HL. The optimal choice of a preferred first-line treatment requires balancing disease control with the occurrence of early and late treatment-related effects. The authors point out that escalated BEACOPP has demonstrated consistently superior progression-free survival but has not shown superior overall survival compared to ABVD.  One meta-analysis did show a small survival improvement (3%) but the risk of increased disease-related acute and long-term toxicity was higher.

The combination of brentuximab vedotin and AVD chemotherapy (A + AVD) is the newest addition to the treatment armamentarium for advanced HL. One trial compared patients with stage 3 or 4 HL being treated with A + AVD (664 patients) to patients receiving standard ABVD (670 patients). Results showed that A + AVD was superior for the endpoint of modified progression-free survival (82.1% and 77.2%, respectively), although there have been some issues in interpreting these results.


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“The key points of my article are that frontline therapy should be individualized on disease-specific and institution specific characteristics,” said Dr Allen. “In community settings where patients cannot be escalated to BEACOPP, [the] initial use of ABVD in low-risk patients or A + AVD is appropriate. If initial treatment with ABVD is utilized it should be PET directed, whereas treatment with A + AVD is not PET directed.”

Optimal Treatment for Elderly Patients With Hodgkin Lymphoma

HL is relatively uncommon in individuals older than 60 years, comprising about 15% to 30% of all cases, and there is no standard treatment. This cohort is considered high risk because of a greater risk of treatment toxicity, underlying comorbidities, and generally higher risk features of the disease. Clinical trials have shown 3-year survival rates of approximately 50% to 70% overall. Due to a particularly high sensitivity to the toxic effects of bleomycin, which have been observed to occur in up to 33% of patients, bleomycin is usually removed from initial therapy or following an interim negative PET. In the GHSG HD 10 and 13 analyses, AVD chemotherapy in early favorable older patients showed poorer disease control as compared to ABVD, although survival was 98%.

Alternative approaches used in favorable risk patients include 2 cycles of ABVD or AVD followed by radiation therapy, and the removal of bleomycin reduced the risk of bleomycin toxicity and decreased grade 3/4 events. Novel combinations of therapy have also been studied with “impressive” results compared with historic controls. Brentuximab monotherapy has been studied in older patients who were not candidates for standard frontline chemotherapy and 92% of patients achieved an objective responsive rate with 73% complete responses. However, the risk of relapse was high and bendamustine or dacarbazine was added, although an unacceptable rate of toxicity with the bendamustine combination resulted in closing that study arm permanently.

“Among elderly patients who are favorable, treatment with a limited number of cycles of AVD and radiation is reasonable,” said Dr Allen. “The novel approaches with brentuximab are preferred in advanced stage disease given their improvement over historical comparators.”

Reference

  1. Allen PB, Winter JN. Controversies in the approach to initial therapy of Hodgkin lymphoma. Curr Oncol Rep. 2019;21(5):39.

This article originally appeared on Hematology Advisor