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Haematological Malignancies Hodgkin’s Lymphoma Brentuximab Vedotin in Relapsed/Refractory Hodgkin’s Lymphoma Eva Domingo-Domenech, 1 Alessandra Comai 2 and Anna Sureda 1 1. Hematology Consultant; 2. Hematology Resident, Hematology Department, Institut Catala d’Oncologia, Hospital Duran I Reynals, Barcelona, Spain Abstract Although most patients diagnosed with Hodgkin’s lymphoma can be considered long-term disease-free survivors with first-line combined modality protocols, some prove to be primary refractory or to have relapsed disease, ultimately dying from the underlying disorder. Brentuximab vedotin (BV) is a monoclonal antibody drug conjugate targetting the CD30 antigen, which is present in the malignant Reed Sternberg cells. Administered as a single drug, it has demonstrated a 34 % rate of complete remission with an objective response rate of 75 % in a population of patients having previously failed autologous stem cell transplantation (ASCT). Side effects of the drug are also manageable, with sensory peripheral neuropathy the most relevant. BV was recently approved for treating patients having relapse after ASCT and those having failed at least two lines of therapy and in whom ASCT is not an option according to both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). BV’s clinical development has recently led to use in much earlier clinical settings. Keywords Hodgkin’s lymphoma, relapsed/refractory disease, autologous stem cell transplantation, allogeneic stem cell transplantation, brentuximab vedotin, CD30 antigen Disclosure: Eva Domingo-Domenech, Alessandra Comai and Anna Sureda have no conflicts of interest to declare. No funding was received in the publication of this article. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 9 December 2014 Accepted: 4 March 2015 Citation: European Oncology & Haematology, 2015;11(1):21–4 Correspondence: Anna Sureda, Hematology Department, Institut Catala d’Oncologia – Hospital Duran I Reynals, Gran Via de l’Hospitalet, 199–203 08908 Barcelona, Spain. E: asureda@iconcologia.net Hodgkin’s lymphoma (HL) is a highly curable haematological malignancy with an overall survival (OS) in the early stages of around 90  % with modern first-line therapies. 1 In patients being diagnosed in advanced stages, the survival rate for 10-year OS is only above 50  %. 2 Despite advances in the treatment of HL, patients having refractory or relapsed (RR) disease still have a poor prognosis. 3 Standard Therapy for Relapsed Hodgkin’s Lymphoma Patients having primary RR disease nowadays remain a clinical challenge. Autologous stem cell transplantation (ASCT) is considered the standard of care for patients having relapsed chemosensitive disease. Two randomised trials showed significant benefit in terms of freedom from treatment failure (FFTF) for ASCT over conventional chemotherapy (CT) in this group of patients. 4,5 These trials have resulted in the recommendation of ASCT at the time of first relapse for even the most favourable of patients, though salvage radiotherapy (RT) can offer an effective treatment for selected subsets. disease and bulky disease at the time of relapse, poor performance status and age ≥50 years. For patients having no risk factors, OS at 5  years was 62  % compared with 37 % and 12  % for those having 1 and ≥2 factors, respectively. Relapsed disease after ASCT represents a clear unmet need. Therapeutic options in this subgroup of patients are heterogeneous and include salvage CT or RT (regardless of whether followed by a second SCT), palliative care, new drugs and biological agents. High-dose CT supported by allogeneic SCT (allo-SCT) is a suitable approach for young and fit patients having chemosensitive disease and who have an human leukocyte antigen (HLA)-compatible donor available. A broad spectrum of evidence supports the existence of a potentially beneficial graft versus HL, with those patients developing chronic graft versus host disease (GvHD) presenting with significantly lower relapse rates after transplantation. Patients relapsing more than 3 years after a first ASCT might be suitable for a second ASCT. 7 Patients with relapsed disease after an allo-SCT represent a major clinical challenge, with no standard of care. Brentuximab Vedotin Patients with HL who relapse after an ASCT have a very poor long-term outcome; there is little information about prognostic factors in this setting. A retrospective analysis of the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT) and Gruppo Italiano Trapianto di Midollo Osseo (GITMO), 6 including 511 adult patients having relapsed HL after ASCT, indicated that after a median follow-up of 49 months, these patients’ OS was 32  % at 5 years; independent risk factors for OS were early relapse after ASCT, stage IV Tou c h MEd ica l MEdia Brentuximab vedotin (BV) (previously known as SNG-35 [Seattle Genetics, WA, US]) is an antibody drug conjugate (ADC) that selectively delivers monomethylauristatin E (MMAE), a very potent antimicrotubule agent, into CD30-expressing cells. Binding MMAE to tubulin disrupts the microtubule network within the cell, subsequently inducing cell-cycle arrest and apoptosis. 8 On 19 August 2011, the US Food and Drug Administration (FDA) granted accelerated approval of BV for two indications in patients having HL: patients who fail an ASCT procedure or patients in whom ASCT 21