Abstract
The CD30 antigen is strongly expressed on neoplastic cells in classical Hodgkin lymphoma (HL), anaplastic large cell lymphoma (ALCL) and other hematologic malignancies (such as DLBCL and cutaneous TCL), while is almost undetectable on healthy tissues, representing an ideal immunotherapeutic target. Since unconjugated anti-CD30 antibody (SGN-30) demonstrated limited clinical activity, researchers’ effort aimed to create an antibody-drug conjugate (ADC), leading to discovery of SGN-35 (brentuximab vedotin), in which an anti-CD30 antibody is linked to the antimitotic agent monomethyl auristatin E (MMAE). In the first phase I study in CD30+ hematologic malignancies (the majority of patients with HL), the maximum tolerated dose was fixed respectively at 1.8mg/Kg every 3 weeks, overall response rate (ORR) and complete response (CR) rate were 38% and 24%. In 2 subsequent phase II studies, amazing results were reported, that permitted accelerated FDA approval for relapsed/refractory patients and led to the development of many clinical trials including BV as first-line HL and ALCL treatment. Moreover, as CD30 antigen may be expressed by other malignancies, the potential therapeutic application is increasing, including at least diffuse large B-cell lymphoma, T-cell lymphomas other than ALCL and cutaneous lymphoproliferative disorders. BV is administrated as outpatient regimen and is usually well tolerated; sensorial peripheral neuropathy represents the most common toxic effect, although it is dose-dependent and at least partially reversible in most cases, after dose reduction and/or treatment ending.
Keywords: Hodgkin lymphomas, anaplastic large cell lymphoma, therapy, brentuximab, vedotin, therapeutic.
Anti-Cancer Agents in Medicinal Chemistry
Title:Therapeutic Use of Brentuximab Vedotin in CD30+ Hematologic Malignancies
Volume: 17 Issue: 7
Author(s): Alberto Fabbri*, Emanuele Cencini, Alessandro Gozzetti, Luana Schiattone and Monica Bocchia
Affiliation:
- Division of Hematology, University of Siena, Siena,Italy
Keywords: Hodgkin lymphomas, anaplastic large cell lymphoma, therapy, brentuximab, vedotin, therapeutic.
Abstract: The CD30 antigen is strongly expressed on neoplastic cells in classical Hodgkin lymphoma (HL), anaplastic large cell lymphoma (ALCL) and other hematologic malignancies (such as DLBCL and cutaneous TCL), while is almost undetectable on healthy tissues, representing an ideal immunotherapeutic target. Since unconjugated anti-CD30 antibody (SGN-30) demonstrated limited clinical activity, researchers’ effort aimed to create an antibody-drug conjugate (ADC), leading to discovery of SGN-35 (brentuximab vedotin), in which an anti-CD30 antibody is linked to the antimitotic agent monomethyl auristatin E (MMAE). In the first phase I study in CD30+ hematologic malignancies (the majority of patients with HL), the maximum tolerated dose was fixed respectively at 1.8mg/Kg every 3 weeks, overall response rate (ORR) and complete response (CR) rate were 38% and 24%. In 2 subsequent phase II studies, amazing results were reported, that permitted accelerated FDA approval for relapsed/refractory patients and led to the development of many clinical trials including BV as first-line HL and ALCL treatment. Moreover, as CD30 antigen may be expressed by other malignancies, the potential therapeutic application is increasing, including at least diffuse large B-cell lymphoma, T-cell lymphomas other than ALCL and cutaneous lymphoproliferative disorders. BV is administrated as outpatient regimen and is usually well tolerated; sensorial peripheral neuropathy represents the most common toxic effect, although it is dose-dependent and at least partially reversible in most cases, after dose reduction and/or treatment ending.
Export Options
About this article
Cite this article as:
Fabbri Alberto*, Cencini Emanuele, Gozzetti Alessandro, Schiattone Luana and Bocchia Monica, Therapeutic Use of Brentuximab Vedotin in CD30+ Hematologic Malignancies, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (7) . https://dx.doi.org/10.2174/1871520616666160902100506
DOI https://dx.doi.org/10.2174/1871520616666160902100506 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Discovery of Lead compounds targeting transcriptional regulation
Transcriptional regulation plays key physiological functions in body growth and development. Transcriptional dysregulation is one of important biomarkers of tumor genesis and progression, which is involved in regulating tumor cell processes such as cell proliferation, differentiation, and apoptosis. Additionally, it plays a pivotal role in angiogenesis and promotes tumor metastasis ...read more
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Innovative targets in medicinal chemistry
Medicinal chemistry continuously evolves in response to emerging healthcare needs and advancements in scientific understanding. This special issue explores the current landscape of innovative targets in medicinal chemistry, highlighting the quest for novel therapeutic avenues. From traditional drug targets such as enzymes and receptors to emerging targets like protein-protein interactions ...read more
Metalloenzymes and Cancer: Μetalloenzyme Ιnhibitors and Artificial Metalloenzymes as anti-cancer agents
Metalloenzymes are enzymes containing metal ions, which are directly bound to the enzyme and play a role in promoting catalysis. About one-third of all enzymes known so far are metalloenzymes [1]. Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Efficacy and Mechanism of Proteasome Inhibitors in Solid Tumor Treatment
Recent Patents on Anti-Cancer Drug Discovery Pyrrolo[2,1-c][1,4]benzodiazepine as a Scaffold for the Design and Synthesis of Anti- Tumour Drugs
Anti-Cancer Agents in Medicinal Chemistry Benzothiazole: A Versatile and Multitargeted Pharmacophore in the Field of Medicinal Chemistry
Letters in Organic Chemistry From Natural Products to Small Molecule Ketone Histone Deacetylase Inhibitors: Development of New Class Specific Agents
Current Pharmaceutical Design Comparison of Tetracycline-regulated Promoters in Lentiviral-based Vectors in Murine Transplantation Studies
Current Gene Therapy Composite Lymphomas: A Challenging Entity
Current Cancer Therapy Reviews Iron Chelators: Development of Novel Compounds with High and Selective Anti-Tumour Activity
Current Drug Delivery Using Insights into Pim1 Structure to Design New Anticancer Drugs
Current Pharmaceutical Design The Prospect of Stem Cells as Multi-Faceted Purveyors of Immune Modulation, Repair and Regeneration in Multiple Sclerosis
Current Stem Cell Research & Therapy Discovery of Small Molecules that Target Autophagy for Cancer Treatment
Current Medicinal Chemistry Cancer and Treatment Modalities
Current Cancer Therapy Reviews Genistein Inhibits Cell Growth and Invasion Through Regulation of miR-27a in Pancreatic Cancer Cells
Current Pharmaceutical Design Epigenetic Modulation: A Promising Avenue to Advance Hematopoietic Stem Cell-Based Therapy for Severe Autoimmune Disorders
Epigenetic Diagnosis & Therapy (Discontinued) Current and Emerging Therapies in Primary Myelofibrosis
Cardiovascular & Hematological Disorders-Drug Targets Epigenetic MicroRNA Regulation of Multiple Chromatin Functions: A Perspective in Cancer
Epigenetic Diagnosis & Therapy (Discontinued) Defensive and Offensive Cross-Reactive Antibodies Elicited by Pathogens: The Good, the Bad and the Ugly
Current Medicinal Chemistry Anti-Cancer Therapy: Targeting the Mevalonate Pathway
Current Cancer Drug Targets Experimental Animal Models of Myocardial Damage in Regenerative Medicine Studies Involving Adult Bone Marrow Derived Stem Cells: Ethical and Methodological Implications
Cardiovascular & Hematological Disorders-Drug Targets Comparison of Sertraline with Rifampin in the treatment of Cholestatic Pruritus: A Randomized Clinical Trial
Reviews on Recent Clinical Trials Using Nutrigenomics to Evaluate Apoptosis as a Preemptive Target in Cancer Prevention
Current Cancer Drug Targets