Antibody–Drug Conjugates in Relapsed/Refractory CD30-positive Lymphomas

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.

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Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress

Journal of Hematology & Oncology ◽

10.1186/s13045-021-01097-z ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Yurou Chu ◽

Xiangxiang Zhou ◽

Xin Wang

Keyword(s):

Therapeutic Index ◽

Essential Elements ◽

Brentuximab Vedotin ◽

Efficacy And Safety ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

Lymphoma Treatment ◽

Novel Targets ◽

Clinical Advances ◽

Antibody Drug

AbstractAntibody-drug conjugates (ADCs) are a promising class of immunotherapies with the potential to specifically target tumor cells and ameliorate the therapeutic index of cytotoxic drugs. ADCs comprise monoclonal antibodies, cytotoxic payloads with inherent antitumor activity, and specialized linkers connecting the two. In recent years, three ADCs, brentuximab vedotin, polatuzumab vedotin, and loncastuximab tesirine, have been approved and are already establishing their place in lymphoma treatment. As the efficacy and safety of ADCs have moved in synchrony with advances in their design, a plethora of novel ADCs have garnered growing interest as treatments. In this review, we provide an overview of the essential elements of ADC strategies in lymphoma and elucidate the up-to-date progress, current challenges, and novel targets of ADCs in this rapidly evolving field.

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Targeting CD30 in Hodgkin Lymphoma: Antibody-Drug Conjugates Make a Difference

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2012.32.83 ◽

2012 ◽

pp. 162-166 ◽

Cited By ~ 1

Author(s):

Catherine S. M. Diefenbach ◽

John P. Leonard

Keyword(s):

Hodgkin Lymphoma ◽

Large Cell ◽

Brentuximab Vedotin ◽

Antibody Drug Conjugate ◽

Lymphoid Malignancies ◽

Drug Conjugates ◽

First Line Therapy ◽

Resistant Disease ◽

Relapsed Disease ◽

Antibody Drug

Overview: CD30 expression is characteristic of the malignant Reed-Sternberg cell in Hodgkin lymphoma (HL) and several other lymphoid malignancies, such as anaplastic large-cell lymphoma (ALCL). Although unconjugated anti-CD30 antibodies have had minimal therapeutic activity in patients with HL as single agents, the CD30-directed antibody-drug conjugate (ADC) brentuximab vedotin has demonstrated activity that has resulted in its recent regulatory approval for the treatment of patients with relapsed HL and ALCL. Approximately 75% of patients with recurrent HL achieve objective responses, with the principal toxicity being peripheral neuropathy. Ongoing studies are evaluating treatment with this agent as part of first-line therapy, for patients with relapsed disease, and for patients with resistant disease and limited other options. Brentuximab vedotin demonstrates the therapeutic value of antibody-drug conjugation and serves as a model of how a novel, targeted approach can be employed to potentially further improve outcomes in settings where curative chemotherapeutic regimens are already available.

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The Pharmaceutical Industry in 2019. An Analysis of FDA Drug Approvals from the Perspective of Molecules

Molecules ◽

10.3390/molecules25030745 ◽

2020 ◽

Vol 25 (3) ◽

pp. 745 ◽

Cited By ~ 23

Author(s):

Beatriz G. de la Torre ◽

Fernando Albericio

Keyword(s):

Natural Products ◽

Pharmaceutical Industry ◽

Small Molecules ◽

Chemical Structure ◽

New Drugs ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

The Us ◽

New Chemical Entities ◽

Antibody Drug

During 2019, the US Food and Drug Administration (FDA) approved 48 new drugs (38 New Chemical Entities and 10 Biologics). Although this figure is slightly lower than that registered in 2018 (59 divided between 42 New Chemical Entities and 17 Biologics), a year that broke a record with respect to new drugs approved by this agency, it builds on the trend initiated in 2017, when 46 drugs were approved. Of note, three antibody drug conjugates, three peptides, and two oligonucleotides were approved in 2019. This report analyzes the 48 new drugs of the class of 2019 from a strictly chemical perspective. The classification, which was carried out on the basis of chemical structure, includes the following: Biologics (antibody drug conjugates, antibodies, and proteins); TIDES (peptide and oligonucleotides); drug combinations; natural products; and small molecules.

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Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma

Journal of Hematology & Oncology ◽

10.1186/s13045-019-0786-6 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 27

Author(s):

Bo Yu ◽

Delong Liu

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Plasma Cells ◽

Immune Therapy ◽

Brentuximab Vedotin ◽

Antibody Drug Conjugates ◽

Lymphoid Malignancies ◽

Drug Conjugates ◽

Promising Treatment ◽

Antibody Drug

Abstract Antibody-drug conjugates (ADC) represent a distinct family of chemoimmunotherapy agents. ADCs are composed of monoclonal antibodies conjugated to cytotoxic payloads via specialized chemical linkers. ADCs therefore combine the immune therapy with targeted chemotherapy. Due to the distinct biomarkers associated with lymphocytes and plasma cells, ADCs have emerged as a promising treatment option for lymphoid malignancies and multiple myeloma. Several ADCs have been approved for clinical applications: brentuximab vedotin, inotuzumab ozogamicin, moxetumomab pasudotox, and polatuzumab vedotin. More novel ADCs are under clinical development. In this article, we summarized the general principles for ADC design, and updated novel ADCs under various stages of clinical trials for lymphoid malignancies and multiple myeloma.

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Antibody-drug conjugates: the chemistry behind empowering antibodies to fight cancer

Hematology ◽

10.1182/asheducation-2013.1.306 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 306-310 ◽

Cited By ~ 19

Author(s):

Jonathan G. Drachman ◽

Peter D. Senter

Keyword(s):

State Of The Art ◽

Rapid Development ◽

Cancer Therapeutics ◽

Brentuximab Vedotin ◽

Magic Bullet ◽

Cytotoxic Therapy ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

Technological Advances ◽

Antibody Drug

Abstract For more than a century, the concept of a “magic bullet” to deliver cytotoxic therapy to the site of disease has been envisioned but only recently have technological advances enabled antibody-drug conjugates to fulfill that dream. The recent approvals of brentuximab vedotin and ado-trastuzumab emtansine and emerging data for many molecules in clinical trials highlight the potential for antibody-drug conjugates to offer new therapeutic options for patients. This chapter reviews the evolution, state of the art, and potential future improvements that are enabling rapid development of this important class of cancer therapeutics.

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An overview of antibody–drug conjugates in oncological practice

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920962997 ◽

2020 ◽

Vol 12 ◽

pp. 175883592096299

Author(s):

Charalampos Theocharopoulos ◽

Panagiotis-Petros Lialios ◽

Helen Gogas ◽

Dimitrios C. Ziogas

Keyword(s):

First Generation ◽

Cancer Therapeutics ◽

Therapeutic Index ◽

General Tendency ◽

Antibody Drug Conjugates ◽

Therapeutic Modalities ◽

Drug Conjugates ◽

The Us ◽

Oncological Practice ◽

Antibody Drug

Antibody–drug conjugates (ADCs) are designed to manipulate the toxic efficacy of specific chemotherapeutic compounds, employing the high affinity of antibody-mediated delivery so as to drive them selectively to target cancer cells. These immunoconjugates encompass the general tendency towards precision medicine and avert the systemic toxicities of conventional chemotherapy, accomplishing an improved therapeutic index. Cumulative experience acquired from first-generation ADCs offers new perspectives to these promising therapeutic modalities for various hematological and solid cancers and propels their clinical development in a faster-than-ever pace, as indicated by the approval of four novel ADCs during the last year. This paper aims to provide an up-to-date overview of the eight ADCs approved by the US Food and Drug Administration and their current indications in oncological practice. Starting from their bio-pharmaceutical background, we track their clinical evolution, with an emphasis on the pivotal trials that led to their commercial release. Late-stage studies examining these eight ADCs in other-than-approved settings as well as the investigation of potential new candidates are also reviewed. In the close future, more data are expected to expand ADCs’ oncological utility and to further reshape their role in cancer therapeutics.

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