In an analysis reported in The Lancet Oncology, Ferdinandus et al found that among patients with newly diagnosed advanced-stage classical Hodgkin lymphoma who were of childbearing potential (POCBP) in the phase III HD21 trial, those receiving BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) had better gonadal function recovery and higher parenthood rates vs those receiving eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone).
The primary analysis of the trial had showed greater efficacy and better acute tolerability with the BrECADD regimen among all patients.
Study Details
The international open-label trial included 1,183 POCBP—defined as women younger than 40 years and men younger than 50 years without baseline gonadal dysfunction—who were randomly assigned between July 2016 and August 2020 to receive BrECADD (248 women, 343 men) or eBEACOPP (243 women, 349 men). Fertility outcomes included gonadal function recovery (via follicle-stimulating hormone [FSH] concentrations), concentrations of anti-Müllerian hormone (AMH; women only) and inhibin B (men only), frequencies of pregnancies, and incidence of parenthood. FSH measurements were available for 767 patients, including 176 women and 201 men in the BrECADD group and 171 women and 219 men in the eBEACOPP group.
Key Findings
Median follow-up was 49.6 months (interquartile range = 39.7–58.4 months).
Gonadal function recovery rates at 4 years among women were 95.3% (95% confidence interval [CI] = 92.0%–98.8%) in the BrECADD group vs 73.3% (95% CI = 66.9%–80.4%) in the eBEACOPP group (hazard ratio [HR] = 1.69, 95% CI = 1.34–2.14); recovery rates at 4 years in men were 85.6% (95% CI = 80.8%–90.8%) in the BrECADD group vs 39.7% (95% CI = 33.6%–46.9%) in the eBEACOPP group (HR = 3.28, 95% CI = 2.51–4.30). AMH and inhibin B concentrations tended to be higher in the BrECADD group.
Pregnancies occurred in 92 female patients and in 36 female partners of male patients. There were 108 reported live childbirths in 99 patients, consisting of 59 in the BrECADD group and 40 in the eBEACOPP group. At 5 years after therapy, the incidence of parenthood for the BrECADD group vs the eBEACOPP group was significantly higher in men (9.3% [95% CI = 6.0%–14.5%] vs 3.3% [95% CI = 1.7%–6.5%], P = .014), but not in women (19.3% [95% CI = 13.7%–27.3%] vs 17.1% [95% CI = 11.9%–24.6%], P = .53).
The investigators concluded: “Compared with eBEACOPP, BrECADD led to significantly better gonadal function recovery, as well as higher parenthood rates (significantly so in men). These findings support BrECADD as preferred first-line therapy, especially for patients wishing to preserve fertility.”
Justin Ferdinandus, MD, of University Hospital Cologne, Cologne, Germany, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Takeda Oncology. For full disclosures of all study authors, visit thelancet.com.
