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Brentuximab Vedotin Plus ABVD or AVD Is Highly Active in Newly Diagnosed Hodgkin Lymphoma

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Key Points

  • The maximum tolerated dose of brentuximab vedotin in combination with ABVD or AVD was not reached.
  • An excess of pulmonary toxicity in the ABVD group indicates that brentuximab vedotin should not be given in combination with bleomycin.
  • Complete remission was achieved in nearly all patients.

Brentuximab vedotin (Adcetris) is active in patients with relapsed/refractory Hodgkin’s lymphoma. In a phase I study reported in The Lancet Oncology, Anas Younes, MD, of Memorial Sloan-Kettering Cancer Center (formerly of The University of Texas MD Anderson Cancer Center), and colleagues evaluated the combination of brentuximab vedotin with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or AVD in patients with previously untreated Hodgkin lymphoma. The maximum tolerated dose of brentuximab vedotin was not reached, and nearly all patients achieved complete remission. However, the combination of brentuximab vedotin and ABVD was associated with excessive pulmonary toxicity, indicating that brentuximab vedotin and bleomycin should not be used together.

Study Details

This open-label dose-escalation study enrolled 51 patients with CD30-positive Hodgkin lymphoma with histologically confirmed stage IIA bulky disease or stage IIB to IV disease and Eastern Cooperative Oncology Group performance status ≤ 2. Patients received brentuximab vedotin at 0.6, 0.9, or 1.2 mg/kg by intravenous infusion every 2 weeks with either ABVD (25 mg/m² doxorubicin, 10 units/m² bleomycin, 6 mg/m² vinblastine, and 375 mg/m² dacarbazine; n = 25) or AVD (ABVD modified regimen without bleomycin; n = 26) for up to six cycles.

Activity and Toxicity

Complete remission was achieved in 21 (95%) of 22 evaluable patients receiving the combination with ABVD and in 24 (96%) receiving the combination with AVD. No dose-limiting toxicities occurred during the first treatment cycle in either group at doses up to the highest brentuximab vedotin study dose of 1.2 mg/kg, and most toxicities were grade 1 or 2. However, pulmonary toxicity occurred in 44% of patients receiving ABVD, including grade 3 to 5 events in 24%, with no pulmonary toxicity observed in the AVD group.

All 12 doses of brentuximab vedotin were received by 60% of patients in the ABVD group and 85% of patients in the AVD group. The most common grade 3 or higher adverse events were neutropenia (80% of ABVD group and 77% of AVD group), pulmonary toxic effects, anemia (20% and 12%), febrile neutropenia (20% and 8%), syncope (12% and 8%), dyspnea (12% and 4%),  pulmonary embolism (12% and 0%), fatigue (4% and 4%), and leukopenia (4% and 4%). Serious adverse events occurred in 56% of patients in the brentuximab vedotin/ABVD group and 27% of the brentuximab vedotin/AVD group, including pulmonary toxic effects (24% and 0%) and febrile neutropenia (16% and 8%).

The investigators concluded, “Brentuximab vedotin should not be given with bleomycin in general or specifically as first-line therapy for patients with treatment naive, advanced stage Hodgkin’s lymphoma. 1.2 mg/kg brentuximab vedotin combined with AVD given every 2 weeks was generally well tolerated by patients.”

A phase III trial comparing brentuximab vedotin plus AVD vs ABVD alone is underway to assess “whether brentuximab vedotin plus AVD might redefine therapy in treatment-naïve patients with Hodgkin lymphoma,” they wrote.

The study was funded by Seattle Genetics Inc and Takeda Pharmaceuticals International Co.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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