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Lymphoma Antibody–Drug Conjugates in Relapsed/Refractory CD30-positive Lymphomas Ulrich Jager 1 and Martin Hutchings 2 1. Professor of Hematology, Medical University of Vienna, Vienna, Austria; Head of the Clinical Department of Hematology and Hemostasis at Vienna General Hospital, Vienna, Austria; 2. Clinical Oncologist, Department of Hematology, Rigshospitalet, Copenhagen, Denmark Abstract Although chemotherapy and radiotherapy are associated with good outcomes in patients with advanced Hodgkin’s lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL), there is a need for alternative approaches to maximise control of the lymphoma in refractory and relapsed cases. Antibody–drug conjugates (ADCs) allow specific targeting of drugs to neoplastic cells. The ADC brentuximab vedotin (BV) has the ability to target cluster of differentiation (CD) 30+ tumour cells and initiate cytotoxic effects. In two phase II trials, BV resulted in objective responses in 75 % and 86 % of patients with refractory or relapsed HL and sALCL, respectively, with an acceptable toxicity profile. Based on these data, BV was granted accelerated approval by the US Food and Drug Administration for the treatment of refractory and relapsed HL and ALCL. A promising indication for BV is acting as a bridge to stem cell transplantation (SCT). Numerous studies are currently examining the role of BV as salvage therapy prior to autologous or allogeneic SCT, as well as in other clinical settings. Keywords Antibody–drug conjugates, brentuximab vedotin, Hodgkin’s lymphoma, systemic anaplastic large cell lymphoma Disclosure: Ulrich Jager has received honoraria and participated in Advisory Boards for Takeda. Martin Hutchings has participated in Advisory Boards for Celgene, Genentech, Janssen and Takeda, and has been a consultant to Genentech and Takeda. Acknowledgements: Medical writing assistance was provided by Katrina Mountfort at Touch Medical Media and funded by Takeda. 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: 23 June 2015 Accepted: 3 September 2015 Citation: European Oncology & Haematology, 2015;11(2):123–9 Correspondence: Ulrich Jager, Medical University of Vienna, Vienna, Spitalgasse 23, 1090 Wien, Austria. E: Martin Hutchings, Department of Haematology, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen, Denmark. E: Support: The publication of this article was supported by Takeda, who were given the opportunity to review the article for scientific accuracy before submission. Any resulting changes were made at the author’s discretion. Antibody-based therapeutics have become an essential component of cancer therapy since the introduction of rituximab in the late 1990s. However, although they can confer clinical benefits, especially when combined with chemotherapy, many monoclonal antibodies do not provide long-term beneficial effects. 1 There is therefore a need to improve the therapeutic efficiency of monoclonal antibodies. Antibody–drug conjugates (ADCs) allow the linking of potent cytotoxic drugs to tumour antigen-specific antibodies, enabling specific targeting of drugs to neoplastic cells while minimising systemic toxicity. ADCs are becoming an increasingly important subclass of antibody-based therapeutics, with 35 ADCs in clinical development in November 2013. 2 Cluster of differentiation (CD) 30 is a transmembrane cytokine receptor protein expressed on certain neoplasms but not normal cells, making it a promising target for therapeutic intervention. Two aggressive lymphoid neoplasms are characterised by strong and uniform expression of CD30: Hodgkin’s lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Early studies of anti-CD30 monoclonal antibodies were promising, although the antibodies had only modest activity as single-agent therapy, 3,4 leading to the development of the anti-CD30 ADC, brentuximab vedotin (BV, Adcetris ® ). Tou ch MEd ica l MEdia This review will focus on the unmet needs in the management of HL and sALCL and discuss clinical studies investigating the efficacy and safety of BV. Current Standard of Care in Hodgkin’s Lymphoma and Systemic Anaplastic Large Cell Lymphoma HL is characterised by the orderly spread of disease from one lymph node to the other. Systemic symptoms are associated with advanced disease. The incidence of HL shows a bimodal age distribution, with the first peak in incidence rates in young adults, and the second peak in older people. 5 It is the most common malignancy in adolescents. 6 Despite the fact that first-line combined chemotherapy regimens, including doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD), achieve durable remission rates in approximately 80 % of cases, 7 a substantial proportion of patients with advanced HL (20–30  %) are refractory to therapy or relapse after initial treatment. 8 Remission rates can be increased by around 10  % with the use of more intensive chemotherapy regimens such as bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP), but this treatment carries the risk of serious adverse events (AEs). 9,10 123