Consolidation therapy with brentuximab vedotin after autologous stem cell transplantation in patients with relapsed/refractory Hodgkin lymphoma

Introduction

The previously published AETHERA study [1] found an improvement in progression-free survival (PFS) with consolidation therapy with brentuximab vedotin in high-risk patients after autologous transplantation with relapsed/refractory Hodgkin lymphoma (HL). At the international symposium, a poster was presented with the results of a study analyzing real-world clinical practice data from seven hematologic intensive care centers in the Czech Republic from January 2015 to December 2021 [2]. The primary objective was to provide basic statistical description and evaluation of the effectiveness and safety of the therapy for the mentioned patient population.

Evaluated patient population

All patients in the study underwent high-dose chemotherapy and autologous stem cell transplantation in the first line of treatment for the first relapse, with each having at least one risk factor defined by the AETHERA study and a negative history of prior therapy with brentuximab vedotin. Data from 39 patients who received brentuximab vedotin therapy at a dose of 1.8 mg/kg body weight administered intravenously every three weeks for a maximum of 16 treatment cycles were included in the analysis.

The median age at the time of the first dose was 37 years (range 19–65). Nearly 80% of patients were initially treated for advanced-stage classical HL, and 59% underwent treatment with the BEACOPP-E regimen (doxorubicin, bleomycin, cyclophosphamide, etoposide, vincristine, prednisone, procarbazine) in the first line of treatment. Primary refractory or early relapsed (within 12 months of the first line of treatment) classical HL was noted in 69% of patients in the analyzed cohort. In 30.8% of patients, two different salvage regimens were administered, and in 64%, failure to achieve a complete treatment response after the salvage regimen before stem cell transplantation was observed.

Results

The median number of treatment cycles with brentuximab vedotin was 8 (range 1–16), with 20.5% of patients undergoing 16 complete cycles of therapy. The main reasons for early treatment discontinuation were neuropathy, relapse, and disease progression, each occurring in 15.4% of cases. A complete response to treatment was recorded in 82% of patients during therapy. During a median follow-up of 28 months, 2-year PFS was 66.2% (95% confidence interval [CI] 0.52–0.85), and 2-year overall survival (OS) was 95% (95% CI 0.82–1.00).

During the study, two patients died, one from disease progression and the other from a severe bacterial infection. Peripheral neuropathy occurred in 38.5% of patients (grades 3–4 in 10.3%), neutropenia in 28.2% (grades 3–4 in 17.9%), and respiratory infections in 28.5% (grades 3–4 in 2.6%).

Conclusion

The results of the study support the view that consolidation therapy with brentuximab vedotin improves progression-free survival in patients with at least one risk factor for subsequent relapse of classical Hodgkin lymphoma, with the therapy showing manageable and plausible toxicity.

(holi)

Sources:
1. Moskowitz C. H., Nademanee A., Masszi T. et al; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 2015; 385 (9980): 1853–1862, doi: 10.1016/S0140-6736(15)60165-9. 
2. Michalka J., Marková J., Gahérová L' et al. P104: Consolidation therapy with brentuximab vedotin after autologous stem cell transplantation for relapsed/refractory Hodgkin lymphoma in the Czech Republic. HemaSphere 2022 Oct; 6: 48–49, doi: 10.1097/01.HS9.0000890984.54786.aa.