Long-Term Follow-Up of the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma Trial

Stefano Luminari, Alexander Fossa, Judith Trotman, Daniel Molin, Francesco d'Amore, Gunilla Enblad, Leanne Berkahn, Sally F Barrington, John Radford, Massimo Federico, Amy A Kirkwood, Peter W M Johnson

Research output: Contribution to journalArticlepeer-review


Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We analyzed long-term results of the response-adapted trial for adult patients with advanced-stage Hodgkin lymphoma. The aim was to confirm noninferiority of treatment de-escalation by omission of bleomycin from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for interim fluorodeoxyglucose positron emission tomography (iPET)-negative patients and assess efficacy and long-term safety for iPET-positive patients who underwent treatment intensification with escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP/BEACOPP14). The median follow-up is 7.3 years. For all patients, the 7-year progression-free survival (PFS) and overall survival (OS) are 78.2% (95% CI, 75.6 to 80.5) and 91.6% (95% CI, 89.7 to 93.2), respectively. The 1.3% difference in 3-year PFS (95% CI, -3.0 to 4.7) between ABVD and doxorubicin, vinblastine, and dacarbazine (AVD) now falls within the predefined noninferiority margin. Among 172 patients with positive iPET, the 7-year PFS was 65.9% (95% CI, 58.1 to 72.6) and the 7-year OS was 83.2% (95% CI, 76.2 to 88.3). The cumulative incidence of second malignancies at 7 years was 5.5% (95% CI, 4.0 to 7.5) for those receiving ABVD/AVD and 2.5% (95% CI, 0.8 to 7.7) for those escalated to BEACOPP. With extended follow-up, these results confirm noninferiority of treatment de-escalation after a negative iPET. Escalation with BEACOPP for iPET-positive patients is effective and safe, with no increase in second malignancies.

Original languageEnglish
Pages (from-to)13-18
Number of pages6
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Issue number1
Early online date26 Oct 2023
Publication statusPublished - 1 Jan 2024


  • Adult
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects
  • Bleomycin/adverse effects
  • Cyclophosphamide/therapeutic use
  • Dacarbazine/adverse effects
  • Doxorubicin/adverse effects
  • Follow-Up Studies
  • Hodgkin Disease/pathology
  • Humans
  • Neoplasms, Second Primary/drug therapy
  • Prednisone/therapeutic use
  • Vinblastine/adverse effects
  • Vincristine/adverse effects


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