Phase II study: Effects of brentuximab vedotin added to first-line therapy for Hodgkin’s lymphoma

Dennis Eichenauer of University Hospital Cologne, Cologne, Germany, and colleagues from the German Hodgkin Study Group (GHSG), published results of a phase II, open label trial examining the effects of adding brentuximab vedotin to standard chemotherapy in newly diagnosed Hodgkin’s lymphoma (HL).  The results were shared in the December 2017 edition of The Lancet Oncology. 

Standard chemotherapy for advanced Hodgkin’s lymphoma includes treatment with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP).  The goal of this trial was to add brentuximab vedotin to standard chemotherapy in 2 different regimens, and observe therapy outcomes. The authors of the study hoped to see reduced toxicities in the modified regimen compared to standard chemotherapy without compromising efficacy (NCT02661503).  The 2 modified regimens prescribed used brentuximab vedotin, etoposide, cyclophosphamide and doxorubicin. The difference in regimens was procarbazine and prednisone (BrECAPP) or dacarbazine and dexamethasone (BrECADD).

Patient Population

• N = 104 patients were enrolled in the study from 20 sites in Germany, two patients were excluded before the start of the study due to acute infection and withdrawn consent
• Median age = 29 years (range 18–60)
• Disease staging
  • II B = 17%
  • III A = 23%
  • III B = 19%
  • IV A = 10%
  • IV B = 31%

Key Findings

• Complete remission after 6 cycles: BrECAPP = 8% (4/48) vs BrECADD = 6% (3/52)
• Partial remission after 6 cycles: BrECAPP = 2% (1/48) vs BrECADD = 4% (2/52)
• No indication for further chemotherapy: BrECAPP = 86% (42/49) vs BrECADD = 88% (46/52)
• Progression-free survival (18-month estimates): BrECAPP = 95% vs BrECADD = 89%

 Adverse Events

• 102 patients were available for toxicity analysis BrECAPP (n = 50) vs BrECADD (n = 52)
• Grade 3 or 4 adverse events
  • Anemia: BrECAPP = 44% vs BrECADD = 35%
  • Thrombocytopenia: BrECAPP = 64% vs BrECADD = 52%
  • Leucopenia: BrECAPP = 88% vs BrEACADD = 85%
  • Infection: BrECAPP = 8% vs BrECADD =15%
  • GI/mucositis: BrECAPP = 10% vs BrECADD = 4%

These study results outline the efficacy of brentuximab vedotin based treatment regimens, combined with chemotherapy.  The proportion of patients who achieved a complete response is comparable to the profile for standard BEACOPP.  The toxicity profile was acceptable and may offer an advantage compared to standard chemotherapy alone. The authors noted that since BrECADD had the most favorable of the two modified regimens, further study is warranted into its use in advanced classical HL. The GHSG have another ongoing trial to further establish that BrECADD has non-inferior efficacy compared with BEACOPP and also reduced toxic side effects (NCT02661503).