Brentuximab-based chemotherapy improves survival and reduces toxicity in patients with advanced Hodgkin lymphoma

1. BrECADD resulted in significantly lower treatment-related morbidity than eBEACOPP.

2. Progression-free survival at 48 months was significantly greater in the BrECADD group compared to the eBEACOPP group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Intensified systemic chemotherapy provides high cure rates, albeit with severe and long-lasting toxicities, in patients with advanced-stage classical Hodgkin lymphoma. The BrECADD regimen (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) aims to reduce these toxicities while maintaining treatment effectiveness compared to current treatment regimens. This randomized controlled trial aimed to compare the tolerability and efficacy of BrECADD with the standard eBEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with newly diagnosed advanced-stage classical Hodgkin lymphoma. The primary outcome of this study was tolerability of treatment, defined as treatment-related morbidity, while the key secondary outcome was progression-free survival. According to study results, the BrECADD demonstrated significantly improved morbidity and progression-free survival compared to the eBEACOPP group. Although this study was well done, it was limited by the open-label design, which could introduce bias in treatment assessment.

Click to read the study in The Lancet

Relevant Reading: Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin’s Lymphoma

In-depth [randomized controlled trial]: Between Jul 22, 2016, and Aug 27, 2020, 1500 patients were assessed for eligibility across 9 countries. Included were patients ≤ 60 years with new-onset, advanced-stage Hodgkin lymphoma (Ann Arbor stage III/IV or stage II with constitutional symptoms). Altogether, 1482 patients (740 in eBEACOPP and 742 in BrECADD) were included in the final analysis. Majority of patients were White (91%) and male (56%). The primary outcome of treatment-related morbidity showed significantly lower rates in the BrECADD group compared to the eBEACOPP group (42% vs. 59%, relative risk [RR] 0.72, 95% confidence interval [CI] 0.65-0.80, p<0.0001). Moreover, the secondary outcome of progression-free survival also favored BrECADD (hazard ratio [HR] 0.66, p=0.035), with higher 4-year progression-free survival rates (94.3% for BrECADD and 90.9% for eBEACOPP). Overall, findings from this study suggest that the BrECADD regimen is more tolerable and more effective than eBEACOPP for first-line treatment of advanced-stage classical Hodgkin lymphoma.

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