Adding Brentuximab to BEACOPP Promising in Relapsed Hodgkin Lymphoma

Use of two different modified BEACOPP regimens that incorporated brentuximab vedotin resulted in improved rates of complete response and complete remission at the end of treatment in a phase II study of patients with relapsed classical Hodgkin lymphoma.

In the study published in Lancet Oncology, Dennis A. Eichenauer, MD, of the University Hospital of Cologne, Germany, and colleagues modified escalated BEACOPP (eBEACOPP; bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) to incorporate brentuximab vedotin, which had been shown to achieve a response in a high proportion of patients with Hodgkin lymphoma. By modifying the protocol they hoped to reduce the burden of treatment while maintaining the outstanding efficacy.

The two regimens were BrECAPP (brentuximab vedotin 1.8 mg/kg on day 1, etoposide 200 mg/m² on days 2–4, doxorubicin 35 mg/m² on day 2, cyclophosphamide 1,250 mg/m² on day 2, procarbazine 100 mg/m² on days 2–8, and prednisone 40 mg/m² on days 2–15) and BrECADD (brentuximab vedotin 1.8 mg/kg on day 1, etoposide 150 mg/m² on days 2–4, doxorubicin 40 mg/m² on day 2, cyclophosphamide 1,250 mg/m² on day 2, dacarbazine 250 mg/m² on days 3–4, and dexamethasone 40 mg on days 2–5).

“The present phase II study investigating the eBEACOPP-based BrECAPP and BrECADD protocols represents a step towards implementation of targeted drugs into the first-line treatment of Hodgkin lymphoma,” the researchers wrote. “However, results of phase III studies testing such novel protocols against current standard chemotherapy regimens are needed to define possible new standard approaches, which is the aim of the randomized German Hodgkin Study Group HD21 study comparing BrECADD and eBEACOPP (NCT02661503).”

The study enrolled 102 patients with newly diagnosed advanced classical Hodgkin lymphoma from 20 sites and randomly assigned them to 6 cycles of either BrECAPP or BrECADD. The co-primary endpoints were complete response to chemotherapy and complete remission at the end of treatment.

After treatment, 86% of patients assigned BrECAPP achieved a complete response after chemotherapy and 94% had complete remission as their final treatment outcome. In the BrECADD group, 88% of patients had both a complete response after chemotherapy and complete remission as their final treatment outcome.

“Although achieving a complete response is an important objective, primary cure is the ultimate goal of treatment,” the researchers wrote. “With the limited median follow-up of 17 months in our study, we can only state that short-term progression-free and overall survival are within the expected range for both eBEACOPP variants.”

The regimens were both well tolerated but the BrECADD regimen had a more favorable toxicity profile. Overall, 58 serious adverse events occurred. The most common grade 3/4 events were hematologic events. Grade 3/4 organ toxic effects were reported in 17% of patients assigned BrECAPP and 4% of patients assigned BrECADD. Grade 1/2 peripheral neuropathy occurred in about one-third of patients in the BrECAPP (32%) and BrECADD (35%) groups, but one patient assigned BrECAPP developed grade 3 peripheral neuropathy.

The authors concluded that both eBEACOPP regimens met the co-primary endpoints, but the BrECADD regimen was chosen to challenge the standard-of-care eBEACOPP regimen in a phase III trial, due to its more favorable toxicity profile.