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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: email@example.com
Martin Hutchings, Department of Haematology, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen, Denmark. E: firstname.lastname@example.org
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
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