Adding Rituximab to Standard Therapy in Interim PET–Positive Advanced Hodgkin Lymphoma
As reported in The Lancet Oncology by Borchmann et al, a phase III German Hodgkin Study Group trial in advanced Hodgkin lymphoma showed no progression-free survival benefit of adding rituximab (Rituxan) in patients with positive positron-emission tomography (PET) findings after two courses (PET-2) of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine [Matulane], and prednisone). Progression-free survival in all PET-2–positive patients was higher than expected.
Study Details
In the open-label trial, 1,100 patients aged 18 to 60 years with newly diagnosed disease were enrolled from 237 sites in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic between May 2008 and May 2011. Of them, 440 had positive PET findings after 2 cycles of escalated BEACOPP and were randomized to receive 6 additional courses of either escalated BEACOPP (n = 220) or rituximab plus escalated BEACOPP (n = 220); rituximab was given at 375 mg/m2 on day 0 and day 3 in cycle 4 and day 1 in cycles 5 to 8. The primary efficacy endpoint was 5-year progression-free survival in the intent-to-treat population.
Outcomes
The current analysis is the second planned interim analysis, and based on the finding of futility by the independent data monitoring committee, it is the final report of the trial.
Median follow-up for progression-free survival was 33 months. Estimated 3-year progression-free survival was 93.0% (95% confidence interval [CI] = 89.4%–96.6%) in the rituximab group vs 91.4% (95% CI = 87.0%–95.7%) in the control group (P =.99). Estimated 3-year overall survival was 94.4% vs 96.5% (P = .31).
Common grade 3 or 4 adverse events included leukopenia (96% vs 95%) and severe infection (20% vs 23%). Treatment-related toxicity resulted in death in three patients in the rituximab group and one patient in the control group, with all deaths due to infection.
The investigators concluded: “The addition of rituximab to BEACOPP-escalated did not improve the progression-free survival of PET-2 positive patients with advanced stage Hodgkin’s lymphoma. However, progression-free survival for PET-2–positive patients was much better than expected, exceeding even the outcome of PET-2–unselected patients in the previous HD15 trial. Thus, PET-2 cannot identify patients at high risk for treatment failure in the context of the very effective German Hodgkin Study Group standard treatment for advanced stage Hodgkin’s lymphoma.”
The study was supported by Deutsche Krebshilfe, the Swiss State Secretariat for Education, Research and Innovation, and Roche Pharma.
Peter Borchmann, MD, of the University Hospital of Cologne, is the corresponding author of The Lancet Oncology article.
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