Brentuximab Vedotin in Pretreated Hodgkin Lymphoma Patients: A Systematic Review and Meta-Analysis

Introduction : The outcome of Hodgkin lymphoma (HL) has improved over the past 20 years. However, the probability of relapse after response to initial treatment is currently approximately 10 to 15 percent for localized HL (i.e. stage I and II) and 20 to 40 percent for advanced stages (i.e. IIIB and IV), dependent on prognostic factors [1]. In young patients eligible for dose intensive chemotherapy, salvage chemotherapy with autologous stem cell transplantation (ASCT) is a frequently used therapy option and can be considered as standard [2, 3]. Patients who relapse following ASCT and those not eligible for myeloablative therapy are being treated with conventional chemotherapy or new novel agents such brentuximab vedotin (BV). Since approval of BV several study groups published the results of their experience in treating refractory/relapsed HL patients with BV.

Patients and methods: The purpose of this study was to evaluate the impact of BV on outcome of patients with refractory and relapsed HL. In this systematic review we analyzed the published data on refractory / relapsed Hodgkin lymphoma patients who received BV as single agent. A systematic literature search was performed and included studies published from 1^st January 2000 to 1^st July 2015 in PubMed, electronic databases EMBASE (Dialog), Cochrane Library, DIMDI-Recherche and MEDPILOT. We used the key words brentuximab, brentuximab vedotein, adcetris, CD30 antibody and SGN-35. Recent conference abstracts from the American Society for Clinical Oncology (ASCO) (2012-2015) and American Society of Hematology (ASH) (2012-2014) were also included. Serial reports of 5 patients and more were included. If several publications from same author and group were published, the publications were re-scanned whether the reported patients' cohorts are the same. We included patients treated with BV pre- and post-transplantation as well as those not eligible for transplantation. Publications reporting about experience with BV in several diseases, e.g. T cell lymphoma and HL, underwent special analysis in order to extract only the HL data. Studies using BV in combination with radiation were disqualified for our analysis.

Results: 51 out of 5369 screened records met the eligibility criteria. After exclusion of duplicates and serial reports with <5 patients total of 22 records (17 full articles and 5 abstracts) were included. Data of 903 patients treated with BV as salvage treatment was collected. The median age of the cohort was 31 year (range: 26-45). The patients received in median 4 lines (range: 1-9) of chemotherapy prior to BV. Median follow up was 16.1 months (range: 4.5-45.1). Most patients were heavily pretreated, 529/903 and 232/903 underwent high dose chemotherapy and autologous stem transplantation or received allogeneic stem transplantation prior of BV respectively. The response rate was 62.7% (range: 30-100%). The complete remission, partial remission, stable disease and progressive disease rates were 31.8%, 35.1%, 19.5% and 11.7% respectively. The one year progression free survival and estimated one year overall survival were 47.7% and 70% respectively.

Conclusion: Significant number of the cohort received autologous and/or allogeneic stem cell transplantation prior BV. Response rate of 62.7% and complete remission rate of 31.8% are supporting results of the pivotal study [4] and establish the solid basis for using BV in heavily pretreated HL patients.

Litreature:

1. Josting, A., et al., New prognostic score based on treatment outcome of patients with relapsed Hodgkin's lymphoma registered in the database of the German Hodgkin's lymphoma study group. J Clin Oncol, 2002. 20 (1): p. 221-30.

2. Sirohi, B., et al., Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma. Ann Oncol, 2008. 19 (7): p. 1312-9.

3. Rancea, M., et al., High-dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma. Cochrane Database Syst Rev, 2013. 6: p. CD009411.

4. Younes, A., et al., Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol, 2012. 30 (18): p. 2183-9.