Positron emission tomography-guided treatment in early-stage favorable Hodgkin lymphoma: Final results of the international, randomized phase III HD16 trial by the German Hodgkin Study Group

Michael Fuchs, Helen Goergen, Carsten Kobe, Georg Kuhnert, Andreas Lohri, Richard Greil, Stephanie Sasse, Max S. Topp, Erhardt Schäfer, Bernd Hertenstein, Martin Soekler, Martin Vogelhuber, Josée M. Zijlstra, Ulrich Bernd Keller, Stefan W. Krause, Martin Wilhelm, Georg Maschmeyer, Julia Thiemer, Ulrich Dührsen, Julia MeissnerAndreas Viardot, Hans Eich, Christian Baues, Volker Diehl, Andreas Rosenwald, Bastian Von Tresckow, Markus Dietlein, Peter Borchmann, Andreas Engert

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PURPOSE: Combined-modality treatment (CMT) with 23 ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and small-field radiotherapy is standard of care for patients with early-stage favorable Hodgkin lymphoma (HL). However, the role of radiotherapy has been challenged. Positron emission tomography (PET) after 23 ABVD (PET-2) might help to predict individual outcomes and guide treatment. METHODS: Between November 2009 and December 2015, we recruited patients age 18 to 75 years with newly diagnosed, early-stage favorable HL for this international randomized phase III trial. Patients were assigned to standard CMT of 23 ABVD and 20-Gy involved-field radiotherapy or PET-guided treatment, omitting involved-field radiotherapy after negative PET-2 (Deauville score, 3). Primary objectives were to exclude inferiority of 10% or more in 5-year progression-free survival (PFS) of ABVD alone compared with CMT in a per-protocol analysis among PET-2-negative patients (noninferiority margin for hazard ratio, 3.01) and to confirm PET-2 positivity (Deauville score $ 3) as a risk factor for PFS among CMT-treated patients. RESULTS: We enrolled 1,150 patients. Median follow-up was 45 months. Among 628 PET-2-negative, per-protocol-treated patients, 5-year PFS was 93.4% (95% CI, 90.4% to 96.5%) with CMT and 86.1% (95% CI, 81.4% to 90.9%) with ABVD (difference 7.3% [95% CI, 1.6% to 13.0%]; hazard ratio, 1.78 [95% CI, 1.02 to 3.12]). Five-year overall survival was 98.1% (95% CI, 96.5% to 99.8%) with CMT and 98.4% (95% CI, 96.5% to 100.0%) with ABVD. Among 693 patients who were assigned to CMT, 5-year PFS was 93.2% (95% CI, 90.2% to 96.2%) among PET-2-negative patients and 88.4% (95% CI, 84.2% to 92.6%) in PET-2-positive patients (P = .047). When using the more common liver cutoff (Deauville score, 4) for PET-2 positivity, the difference was more pronounced (5-year PFS, 93.1% [95% CI, 90.7% to 95.5%] v 80.9% [95% CI, 72.2% to 89.7%]; P = .0011). CONCLUSION: In early-stage favorable HL, a positive PET after two cycles ABVD indicates a high risk for treatment failure, particularly when a Deauville score of 4 is used as a cutoff for positivity. In PET-2-negative patients, radiotherapy cannot be omitted from CMT without clinically relevant loss of tumor control.

Original languageEnglish
Pages (from-to)2835-2845
Number of pages11
JournalJournal of clinical oncology
Issue number31
Publication statusPublished - 1 Jan 2019

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