Escalated BEACOPP Plus Rituximab in Advanced Hodgkin Lymphoma Fails to Improve Outcomes

Adding rituximab to an escalated regimen of BEACOPP did not improve progression-free survival in patients with advanced-stage Hodgkin lymphoma, according to the results of the phase III HD18 trial by the German Hodgkin Study Group.

The study, which was published recently in Lancet Oncology, was also designed to determine if a PET scan after the second cycle of BEACOPP_escalated could identify patients at high risk for treatment failure. However, results showed that it did not identify these patients.

“Unexpectedly, a positive PET after two courses of BEACOPP_escalated did not identify a high-risk patient cohort in our phase III trial,” wrote Peter Borchmann, MD, of the department of nuclear medicine at the University Hospital of Cologne, Germany, and colleagues. “Accordingly, addition of rituximab to improve the presumably poor progression-free survival did not show any efficacy over standard treatment with BEACOPP_escalated followed by radiotherapy to PET-positive residual disease.”

According to the study, previous research had suggested that interim PET scans during chemotherapy are superior to baseline international prognostic scoring for predicting long-term treatment outcomes in patients with Hodgkin lymphoma. Therefore, Borchmann and colleagues tested if early interim PET imaging could be used to guide treatment for these patients.

The international study included 1,100 patients aged 18 to 60 years with newly diagnosed, advanced-stage Hodgkin lymphoma. Patients underwent PET imaging after completing two cycles (PET-2) of BEACOPP_escalated and were centrally assessed by an expert panel. Those patients with a positive PET-2 were randomly assigned to six additional courses of BEACOPP_escalated with or without rituximab. The primary efficacy outcome was 5-year progression-free survival in the intent-to-treat population.

Of the 1,110 patients enrolled, 440 patients had positive PET-2 scans and were then randomized.

With a median follow-up of 33 months, the estimated 3-year progression-free survival was 91.4% for patients in the BEACOPP_escalated arm compared with 93% for patients in the rituximab arm.

“The study missed its primary objective to show a progression-free survival benefit of the combined immuno-chemotherapy,” the researchers wrote.  “Because high-risk patients in our trial were identified by PET-positivity after two cycles of standard chemotherapy, rituximab could not be applied during these first two cycles. Therefore, we cannot conclude on an overall efficacy of rituximab in the treatment of Hodgkin lymphoma from our trial. Nonetheless, there is certainly no benefit when added to BEACOPP_escalated in PET-2–positive patients.”

The most common grade 3/4 adverse events were leucopenia and severe infections. Fatal treatment-related toxic effects occurred in one patient in the BEACOPP_escalated group and three patients in the rituximab group.

An independent data monitoring committee recommended the publication of this second interim analysis as the final results of the study.

In an editorial published with the study, Michael Crump, MD, of Princess Margaret Cancer Centre, Toronto, wrote: “The results of the HD18 trial tell us that, at least with intensive chemotherapy like BEACOPP_escalated, there is no value in altering treatment based on a positive PET-2 scan; the ability to reduce treatment for those with a negative PET-2 scan, with the goal of decreasing toxic effects while maintaining efficacy, awaits additional data from this study.”