As reported in the Journal of Clinical Oncology by Fuchs et al, final results of the German Hodgkin Study Group phase III HD16 trial in early-stage favorable Hodgkin lymphoma indicate that combined modality therapy (CMT) is associated with better progression-free survival vs chemotherapy alone among patients with negative positron-emission tomography (PET) findings after two cycles of chemotherapy (PET-2). PET-2 positivity was associated with poorer progression-free survival among all patients receiving CMT.

“In early-stage favorable [Hodgkin lymphoma], a positive PET [scan] 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.”

— Fuchs et al

Tweet this quote

Study Details

In the trial, 1,150 patients from sites in Germany, Switzerland, Austria, and the Netherlands with newly diagnosed early-stage favorable Hodgkin lymphoma were enrolled between November 2009 and December 2015. Patients were randomly assigned to CMT consisting of two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and involved-field radiotherapy (IFRT) at 20 Gy (n = 575) or PET-guided treatment that consisted of two cycles of ABVD for all patients and IFRT at 20 Gy only for those with positive PET-2 findings (ie, radiotherapy omitted in those with negative PET-2, defined as Deauville score < 3).

Primary study objectives were to exclude inferiority of 10% or more in 5-year progression-free survival with ABVD alone compared with CMT in per-protocol analysis among PET-2–negative patients using a noninferiority margin of 3.01 for the hazard ratio; and to assess PET-2 positivity (Deauville score ≥ 3) as a risk factor for progression-free survival among patients receiving CMT.

Progression-Free Survival by PET-2 Status

Median follow-up was 45 months. Among 628 PET-2–negative patients in the per-protocol analysis (328 in the CMT group and 300 in the PET-guided group), 5-year progression-free survival was 93.4% with CMT and 86.1% with ABVD (difference = 7.3%, 95% confidence interval [CI] = 1.6%–13.0%). The hazard ratio was 1.78, with a 95% CI  of 1.02–3.12, which included the predefined noninferiority margin of 3.01; noninferiority of the PET-2–guided omission of radiotherapy was thus not shown. Five-year overall survival was 98.1% with CMT and 98.4% with ABVD.

Among all 693 patients who received CMT (353 PET-2–negative and 148 PET-2–positive patients in the CMT group plus 192 PET-2–positive patients in the PET-guided group), 5-year progression-free survival was 93.2% among PET-2–negative patients vs 88.4% among PET-2–positive patients (P = .047). When a Deauville score of 4 was used for PET-2 positivity, 5-year progression-free survival was 93.1% among PET-2–negative patients vs 80.9% among PET-2–positive patients (P = .0011).

The investigators concluded, “In early-stage favorable [Hodgkin lymphoma], a positive PET [scan] 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.”

Andreas Engert, MD, of the German Hodgkin Study Group, University Hospital of Cologne, is the corresponding author for the Journal of Clinical Oncology article.  

Disclosure: The study was funded by Deutsche Krebshilfe grants and the Swiss State Secretariat for Education, Research, and Innovation. For full disclosures of the study authors, visit jco.ascopubs.org.