Universität zu Köln

Ferdinandus, Justin ORCID: 0000-0002-3481-7997, Schneider, Gundolf, Moccia, Alden, Greil, Richard, Hertzberg, Mark, Schaub, Valdete, Hüttmann, Andreas, Keil, Felix, Dierlamm, Judith, Hänel, Mathias, Novak, Urban, Meissner, Julia, Hellmuth, Johannes Christian, Mathas, Stephan, Zijlstra, Josée M, Fosså, Alexander, Viardot, Andreas, Hertenstein, Bernd, Martin, Sonja, Giri, Pratyush, Kamper, Peter, Molin, Daniel, Jablonski, Janina ORCID: 0009-0007-2811-4762, Damaschin, Carla, Robertz, Anne Sophie, Rosenbrock, Johannes ORCID: 0000-0003-3340-0556, Fuchs, Michael ORCID: 0000-0003-3289-3272, Borchmann, Peter ORCID: 0000-0003-3782-2158 and Behringer, Karolin ORCID: 0000-0002-7035-1784 (2025). Fertility in patients with advanced-stage classic Hodgkin lymphoma treated with BrECADD versus eBEACOPP: a secondary analysis of the multicentre, randomised, parallel, open-label, phase 3 HD21 trial. The Lancet Oncology, 26 (8). pp. 1081-1090. Elsevier. ISSN 1470-2045

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Abstract

Background: BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) has shown higher efficacy and better acute tolerability than eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in newly diagnosed, advanced-stage classic Hodgkin lymphoma. In this secondary analysis of the HD21 trial, we aimed to compare gonadal function recovery and fertility outcomes between these two regimens. Methods: In the multicentre, parallel, open-label, phase 3 HD21 trial, conducted across 233 trial sites in nine countries, patients aged 18–60 years with newly diagnosed, advanced-stage classic Hodgkin lymphoma and an Eastern Cooperative Oncology Group performance status of 0–2 were randomly assigned (1:1) to receive 4–6 cycles of eBEACOPP or BrECADD, guided by interim response. Patients and investigators were not masked to treatment assignment. Primary outcomes were progression-free survival and treatment-related morbidity (reported elsewhere). Here we report an unplanned analysis of fertility outcomes. 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. Gonadal function recovery, AMH, and inhibin B were assessed in the patients of childbearing potential (POCBP) cohort, which included women younger than 40 years and men younger than 50 years without baseline gonadal dysfunction. Pregnancy and parenthood analyses also included patients with baseline gonadal dysfunction. The HD21 trial was registered at ClinicalTrials.gov (NCT02661503) and is ongoing but closed to enrolment. Findings: Between July 22, 2016, and Aug 27, 2020, 1183 POCBP were enrolled (592 in the eBEACOPP group, 591 in the BrECADD group; 692 men, 491 women). FSH measurements were available for 767 patients (420 men and 347 women). Median follow-up was 49·6 months (IQR 39·7–58·4). BrECADD was associated with significantly higher 4-year gonadal function recovery rates compared with eBEACOPP (95·3% [95% CI 92·0–98·8] in the BrECADD group vs 73·3% [66·9–80·4] in the eBEACOPP group, HR 1·69 [95% CI 1·34–2·14] in women; 85·6% [80·8–90·8] vs 39·7% [33·6–46·9], HR 3·28 [2·51–4·30] in men). AMH and inhibin B concentrations were generally higher in the BrECADD group compared with the eBEACOPP group. A total of 92 pregnancies were reported among female patients, and 36 among partners of male patients. These led to 108 reported childbirths in 99 patients (59 in the BrECADD group and 40 in the eBEACOPP group). After therapy, 5-year incidence of parenthood was significantly higher in men (9·3% [95% CI 6·0–14·5] vs 3·3% [1·7–6·5], p=0·014), but not significantly higher in women (19·3% [13·7–27·3] vs 17·1% [11·9–24·6], p=0·53) with BrECADD versus eBEACOPP. Interpretation: 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.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Ferdinandus, Justin UNSPECIFIED https://orcid.org/0000-0002-3481-7997 UNSPECIFIED Schneider, Gundolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Moccia, Alden UNSPECIFIED UNSPECIFIED UNSPECIFIED Greil, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Hertzberg, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaub, Valdete UNSPECIFIED UNSPECIFIED UNSPECIFIED Hüttmann, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Keil, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Dierlamm, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Hänel, Mathias UNSPECIFIED UNSPECIFIED UNSPECIFIED Novak, Urban UNSPECIFIED UNSPECIFIED UNSPECIFIED Meissner, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellmuth, Johannes Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Mathas, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Zijlstra, Josée M UNSPECIFIED UNSPECIFIED UNSPECIFIED Fosså, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Viardot, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hertenstein, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Giri, Pratyush UNSPECIFIED UNSPECIFIED UNSPECIFIED Kamper, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Molin, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Jablonski, Janina UNSPECIFIED https://orcid.org/0009-0007-2811-4762 UNSPECIFIED Damaschin, Carla UNSPECIFIED UNSPECIFIED UNSPECIFIED Robertz, Anne Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenbrock, Johannes UNSPECIFIED https://orcid.org/0000-0003-3340-0556 UNSPECIFIED Fuchs, Michael UNSPECIFIED https://orcid.org/0000-0003-3289-3272 UNSPECIFIED Borchmann, Peter UNSPECIFIED https://orcid.org/0000-0003-3782-2158 UNSPECIFIED Behringer, Karolin UNSPECIFIED https://orcid.org/0000-0002-7035-1784 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-804575
Identification Number:	10.1016/S1470-2045(25)00262-1
Journal or Publication Title:	The Lancet Oncology
Volume:	26
Number:	8
Page Range:	pp. 1081-1090
Number of Pages:	10
Date:	August 2025
Publisher:	Elsevier
ISSN:	1470-2045
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Innere Medizin > Klinik I für Innere Medizin - Hämatologie und Onkologie Faculty of Medicine > Weitere > Centrum für integrierte Onkologie (CIO)
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80457