Brentuximab with AVD – pro
The rationale for brentuximab in Hodgkin’s is that the Reed-Sternberg cells of classical Hodgkin lymphoma typically express CD30, which is targeted by brentuximab vedotin, an anti-CD30 monoclonal antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E. Brentuximab with AVD was studied recenlty by Younis et al and there were twoa rms,once that also included bleomycin. The belomycin arm produced unacceptabel pulmoinary toxicity but 1·2 mg/kg brentuximab vedotin combined with AVD given every 2 weeks was generally well tolerated by patients. At present, a phase 3 trial comparing brentuximab vedotin plus AVD to ABVD alone is ongoing (ClinicalTrials.gov, number NCT01712490) and will formally assess whether brentuximab vedotin plus AVD might redefine therapy in treatment-naive patients with Hodgkin’s lymphoma.
At the 2014 ASH Annual Meeting, Dr. Connors and colleagues reported safety and efficacy results for 51 newly diagnosed advanced-disease (80% stage III/IV) patients who received brentuximab vedotin in combination with ABVD or the same regimen without bleomycin (AVD) in a multicenter dose-escalation study. Patients received doses of 0.6, 0.9, or 1.2 mg/kg of brentuximab vedotin with standard doses of ABVD or 1.2 mg/kg with AVD on days 1 and 15 of each 28-day cycle for up to six cycles of therapy.
95% of patients given ABVD and brentuximab vedotin achieved a complete response, as did 96% of patients given AVD and brentuximab vedotin. However, toxicity was a concern with the ABVD regimen. Pulmonary toxicity occurred in 11 patients.
The same group analyzed AVD and brentuximab and presented their results at 2015 ASCO. The combination of AVD and brentuximab vedotin led to complete responses in 96% of 50 patients, a 3-year failure-free survival rate of 92%, and a 3-year overall survival rate of 100%. Responses to AVD (or ABVD) were durable. At a median follow-up of 40 months, the longest time to relapse was 22 months; 96% of patients have been followed longer than 22 months.
Anas Younes et al, Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin’s lymphoma: a phase 1, open-label, dose-escalation study. Lancer Oncology, Volume 14, No. 13, p1348–1356, December 2013
ASH 2014, 292 Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long Term OutcomesClinically Relevant Abstract
Program: Oral and Poster Abstracts
Type: Oral Session: 624.
Connors JM, Ansell S, Park SI, et al: Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed advanced stage Hodgkin lymphoma: Long-term outcomes. 2014 ASH Annual Meeting. Abstract 292. Presented December 8, 2014.
Forero-Torres A, Holkova B, Sharman JP, et al: Brentuximab vedotin monotherapy and in combination with dacarbazine in frontline treatment of Hodgkin lymphoma in patients aged 60 years and above: Interim results of a phase 2 study. 2014 ASH Annual Meeting. Abstract 294. Presented December 8, 2014.
Busia A, Laffranchi A, Viviani S, Bonfante V, Villani F.Cardiopulmonary toxicity of different chemoradiotherapy combined regimens for Hodgkin’s disease. Anticancer Res. 2010 Oct;30(10):4381-7.