Final Results of German Trial of PET-Guided Treatment in Advanced Hodgkin Lymphoma


Key Points

  • The addition of rituximab to eBEACOPP did not improve progression-free survival among patients with advanced Hodgkin lymphoma and positive PET-2 results.
  • In PET-2–negative patients, the 4 × eBEACOPP regimen was associated with noninferior progression-free survival and improved overall survival.

Final results of the German Hodgkin Study Group phase III HD18 trial, reported in The Lancet by Borchmann et al, showed no benefit of adding rituximab (Rituxan) to escalated BEACOPP (eBEACOPP; bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with advanced Hodgkin lymphoma and positive positron-emission tomography conducted after 2 cycles of eBEACOPP (PET-2).  However, the investigators did observe a benefit to reducing eBEACOPP to 4 cycles in patients with negative PET-2 results.

Study Details

In the open-label trial, patients aged 18 to 60 years with newly diagnosed advanced disease from 301 sites in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic were randomized between May 2008 and July 2014 to receive treatment based on PET-2 results after 2 cycles of eBEACOPP. Patients with positive PET-2 were randomized to receive six additional

cycles of either standard eBEACOPP (8 × eBEACOPP) or eBEACOPP with rituximab (8 × R-eBEACOPP). Those with negative PET-2 were randomized between standard treatment with six additional cycles of eBEACOPP (8 × eBEACOPP) or experimental treatment with two additional cycles (4 × eBEACOPP). After a protocol amendment in June 2011, patients with positive PET-2 were no longer randomized and were assigned to receive 6 × eBEACOPP, and patients with negative PET-2 were randomized to 6 × eBEACOPP or 4 × eBEACOPP. The primary endpoint was progression-free survival, with testing for superiority in the PET-2–positive cohort and noninferiority in the PET-2–negative cohort.

Survival Outcomes

Among patients with positive PET-2, 5-year progression-free survival was 89.7% among 217 in the eBEACOPP group vs 88.1% among 217 in the rituximab plus eBEACOPP group (P = .46). Estimated 5-year overall survival was 96.4% vs 93.9% (P = .25).

Among patients with negative PET-2, 5-year progression-free survival was 90.8% among 504 patients receiving either 8 × eBEACOPP or 6 × eBEACOPP vs 92.2% among 501 patients receiving 4 × eBEACOPP (hazard ratio = 0.79, 95% confidence interval = 0.50–1.24), with the noninferiority margin of 6% difference in 5-year progression-free survival not being exceeded. Estimated 5-year overall survival was 95.4% vs 97.7% (P = .0037).


The 4 × eBEACOPP regimen was associated with a lower incidence of severe infection (8% vs 15%) and organ toxicity (8% vs 18%). Of 10 treatment-related deaths, 1 (< 1%) occurred in the 8 × eBEACOPP group and 3 (1%) occurred in the rituximab group in the PET-2–positive cohort and 6 (1%) occurred in the 8 × eBEACOPP or 6 × eBEACOPP group in the PET-2–negative cohort.

The investigators concluded: “The favourable outcome of patients treated with eBEACOPP could not be improved by adding rituximab after positive PET-2. PET-2 negativity allows reduction to only four cycles of eBEACOPP without loss of tumour control. PET-2-guided eBEACOPP provides outstanding efficacy for all patients and increases overall survival by reducing treatment-related risks for patients with negative PET-2. We recommend this PET-2-guided treatment strategy for patients with advanced-stage Hodgkin’s lymphoma.”

The study was funded by Deutsche Krebshilfe, Swiss Secretariat for Education and Research, and Roche Pharma AG.

Peter Borchmann, MD, of the University Hospital of Cologne, is the corresponding author of The Lancet article. 

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