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.
