-Author name in bold denotes the presenting author
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3057 Comprehensive Analysis of Treatment Related Morbidity and Progression -Free Survival in the GHSG Phase III HD21 TrialClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
clinical trials, Research, Hodgkin lymphoma, Lymphomas, Clinical Research, Diseases, Therapies, Lymphoid Malignancies, survivorship
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Peter Borchmann1, Alden Moccia, MD2*, Richard Greil, MD3, Gundolf Schneider, M.Sc.4*, Mark S. Hertzberg, MD5, Valdete Schaub6*, Andreas Huettmann, MD7*, Felix Keil8*, Valdete Schaub9*, Mathias Hänel, MD10, Urban Novak, MD11*, Julia Meissner, MD12*, Andreas Zimmermann13*, Stephan Mathas14*, Josée M Zijlstra15*, Alexander Fosså, MD16*, Andreas Viardot, MD PhD17, Bernd Hertenstein, MD18*, Sonja Martin19*, Pratyush Giri, MBBS20*, Peter Kamper, MD, PhD21*, Daniel L. Molin, MD22*, Stefanie Kreissl23*, Justin Ferdinandus, MD1,4*, Michael Fuchs, MD24*, Andreas Rosenwald25*, Wolfram Klapper26*, Hans Eich27*, Christian Baues28*, Michael Hallek, MD29*, Markus Dietlein28*, Carsten Kobe, MD30* and Volker Diehl, MD31

1German Hodgkin Study Group, Cologne, Germany
2Medical Oncology, Oncology Institute of Southern Switzerland, EOC, Locarno, Switzerland
3Paracelsus Medical University, Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Salzburg, Austria
4Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
5Prince of Wales Hospital and University of New South Wales, Sydney, Australia
6Clinic II of Internal Medicine, Universital Hospital of Tuebingen, Tuebingen, Germany
7Department of Hematology, Essen University Hospital, Essen, Germany
8OEGK Hanusch Hospital, Vienna, Austria
9Clinic II for Internal Medicine, Universital Hospital of Hamburg, Hamburg, Germany
10Department of Internal Medicine III, Hematology, Oncology and Cellular Therapies, Hospital Chemnitz, Chemnitz, Germany
11The Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland
12Medicine V, University Hospital of Heidelberg, Heidelberg, Germany
13Hospital Leverkusen, Leverkusen, Germany
14Charité Berlin, Berlin, DEU
15Department of hematology, Amsterdam UMC, Amsterdam, Netherlands
16Department of Oncology, Oslo University Hospital, Oslo, Norway
17Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
18Department of Internal Medicine I, Klinikum Bremen Mitte, Bremen, Germany
19Robert-Bosch-Hospital, Stuttgart, Germany
20Royal Adelaide Hospital, Adelaide, Australia
21Department of Hematology, Aarhus University Hospital, Aarhus, Denmark
22Oncology Department, Uppsala University, Uppsala, Sweden
23Hospital Ordensklinikum Linz, Linz, Austria
24Department I of Internal Medicine, German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany
25University Hospital of Wuerzburg, Würzburg, Germany
26Department of Pathology, University Hospital Schleswig-Holstein, Kiel, DEU
27Munster University, -, DEU
28University Hospital of Cologne, Cologne, DEU
29Center of Integrated Oncology Aachen Bonn Cologne Duesseldorf (ABCD), University Hospital Cologne, Cologne, Germany, Cologne, Germany
30Department of Nuclear Medicine, German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany
31GHSG, Cologne, Germany


The GHSG-HD21 trial for newly diagnosed adult patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) compares the BrECADD regimen (Brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) to eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procar­bazine, prednisone) in a PET adapted approach. Separate analyses of the co-primary endpoints for tolerability and efficacy demonstrated a significant and relevant reduction in treatment-related morbidity (TRMB) and non-inferiority of PFS, respectively. Here, we report the first combined comprehensive analysis of the primary endpoints of the HD21 trial.


This international open-label phase III trial included adult patients aged ≤ 60 yrs with AS-cHL. Patients were randomized in a 1:1 ratio to PET2-guided 4-6 21-day cycles of either eBEACOPP or BrECADD. PET2 and PFS events were assessed by blinded panel review. At a planned interim analysis at 36 months follow-up, the efficacy endpoint PFS was determined in the ITT cohort comprising 1,482 patients (eBEACOPP n=740, and BrECADD n=742) while the safety endpoint TRMB was determined in 1,470 patients (BEACOPP n=732, and BrECADD n=738). Subgroup analyses were calculated with 95% confidence intervals (Cis). The trial was registered at clinicaltrials.gov (NCT02661503) and conducted according to ICH-GCP guidelines.


Between July 2016 and August 2020, we enrolled 1,500 patients from 9 countries across 233 trial sites. Actual median follow-up for this analysis was 40 months. Baseline characteristics were well balanced between treatment arms, median age was 34 yrs (range 18-61), and 47% were high-risk (international prognostic index IPS ≥ 3).

Overall, the relative risk for a TRMB event was 0.72 (95% CI, 0.65-0.79) in favor of BrECADD. Subgroup analyses confirmed a consistent, highly significant TRMB benefit in all relevant subgroups. Dose reductions were required less frequently with BrECADD than with eBEACOPP (figure 1); full dose treatment at cycle 4 was administered in 58.5% of patients in the eBEACOPP group compared to 77.8% in the BrECADD group. In PET2-positive patients at cycle 6, full dose treatment was received by 42.5% in the eBEACOPP group versus 67.3% in the BrECADD group. Most frequent reasons for dose reductions were leukopenia for eBEACOPP (in 33.7% of patients) and thrombocytopenia for BrECADD (in 23.1 % of patients).

59% of patients achieved a PET2-negative response and were treated with a total of 4 cycles in each group; conversely, 41% of patients were PET2-positive and received 6 cycles. At the end of treatment with either 4 or 6 cycles, a complete metabolic response was seen in 80% and 82% of patients in the eBEACOPP and BrECADD cohorts, respectively. The 3-yr PFS was 94.9% for BrECADD (95% CI 93.5% - 96.7%), and 92.3% for eBEACOPP (95% CI 90.3% - 94.3%), with a corresponding HR of 0.63 (95% CI 0.42-0.94). A HR favoring BrECADD was consistently observed across all relevant subgroups (figure 2). Notably, HRs favoring BrECADD were generally lower in lower-risk cohorts including IPS (0, 1; 2, 3; 4-7: HR 0.45, 0.59, 0.87, respectively), stage (Ann-Arbor stage II, III, IV: HR 0.35, 0.6, 0.78, respectively), or PET-2 response (negative versus positive, HR 0.4, 95% CI 0.21-0.76 vs 0.78, 95% CI 0.44-1.38). Corresponding 3-yr PFS rates for BrECADD versus eBEACOPP were 97.1% (95% CI 95.5% - 98.7%) versus 93.6% (95% CI 91.3% - 95.9%) for PET2-negative patients and 93.5% (95% CI 90.6% - 96.5%) versus 90.6% (95% CI 87.1% - 94.1%) for PET2-positive patients, respectively.


With the novel BrECADD regimen, we observed the highest 3-yr PFS rates reported to date in a randomized clinical trial in advanced-stage cHL. Our analyses suggest that the unexpectedly high and improved efficacy of the new BrECADD regimen compared to eBEACOPP is a direct consequence of its improved tolerability and deliverability. Importantly, while the larger patient cohort of PET2-negative patients achieves a very high 3-yr PFS of 97% with a very short and safe 12-week treatment, this benefit was also observed for PET2-positive patients. In conclusion, the optimized risk-benefit ratio of the BrECADD regimen combined with the individualized PET2-guided treatment duration sets a new benchmark for the treatment of adult patients with newly diagnosed advanced stage cHL

Disclosures: Borchmann: Bristol-Myers Squibb: Consultancy; Merck Sharp & Dohme: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda Oncology: Consultancy, Research Funding; MPI: Research Funding. Greil: Roche: Honoraria, Research Funding. Hänel: Novartis, SOBI, Gilead, Falk Foundation: Honoraria; Novartis, BMS/Celgene, Gilead, Pfizer, Incyte, Sanofi/Aventis, Roche, Amgen, SOBI, Janssen: Consultancy. Novak: Novartis: Other: Advisory Boards; Gilead: Other: Advisory Boards; BMS: Other: Advisory Board. Viardot: F. Hoffmann-La Roche Ltd, Abbvie, Kite/Gilead, BMS: Honoraria; BMS: Research Funding; F. Hoffmann-La Roche Ltd, Abbvie, Kite/Gilead, BMS: Consultancy. Giri: Royal Adelaide Hospital: Current Employment. Molin: MSD: Honoraria; Roche: Honoraria; BMS: Honoraria; Takeda: Honoraria. Ferdinandus: Roche: Honoraria. Hallek: Abbvie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding.

OffLabel Disclosure: USe of Brentuximab vedotin in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone for advacned stage classical HL

*signifies non-member of ASH