Brentuximab vedotine

Author:Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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CAS number: 914088-09-8

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DefinitionThis section has been translated automatically.

Brentuximab Vedotin is an antibody-drug conjugate (ADC) with a monoclonal antibody directed against human CD30 antigen. The antibody is covalently bound to 3-5 molecules of the cytostatic drug monomethylauristatin E. Brentuximab Vedotin has been approved in the European Union since October 2012 for the treatment of Hodgkin's lymphoma and anaplastic large cell lymphoma. Since the end of 2017, the indication has been extended to CD30 positive cutaneous T-cell lymphoma. Brentuximab Vedotin hasorphan drug status for rare diseases.

Spectrum of actionThis section has been translated automatically.

The property of monoclonal antibodies to specifically recognize certain cell characteristics can also be used in oncological therapy: antibodies are supposed to detect the tumor cells and transport the cytostatic drug specifically to the tumorous target cell. The antibody-drug conjugate is fixed to the surface of the CD30 positive tumor cell. The antibody-drug conjugate is then introduced into the cell. There the conjugate is enzymatically cleaved; the cytostatic drug (monomethylauristatin E) can unfold its effectiveness by destroying the mitotic spindle. This leads to G2/M cell cycle arrest and apoptosis of the cell.

IndicationThis section has been translated automatically.

Brentuximab Vedotine was tested in two pivotal Phase II studies in 160 patients in the USA, Canada and Europe, 102 of whom had Hodgkin's lymphoma and 58 of whom had sALCL. In the Hodgkin's lymphoma study, all 102 patients had already received high-dose chemotherapy with autologous stem cell transplantation (ASCT) and were pretreated with multiple chemotherapy regimens. Brentuximab Vedotine was given for a maximum of 16 cycles. 96 % of patients achieved disease control (i.e. remission or disease stabilization), 94 % of patients showed tumor reduction and 75 % of patients had an objective overall response (ORR = partial or complete remission) (Younes A et al. 2012)

In the sALCL study, 58 patients who had failed at least one previous combination chemotherapy received Brentuximab Vedotin for a maximum of 16 cycles. Here, 97% of the patients achieved tumour reduction and 86% of the patients achieved an objective overall response (ORR = partial or complete remission).

In the pivotal randomized, multicenter ALCANZA study, which was conducted in 13 European countries in patients with cutaneous T-cell lymphoma (Prince HM et al. 2017), 131 participants with pretreated mycosis fungoides and primary anaplastic large cell lymphoma were treated with Brentuximab Vedotine or with oral methotrexate or Bexarotene. At least 10% of the tumor cells had to express CD30. After a median follow-up of 22.9 months, progression-free survival was 16.7 months in the Brentuximab vedotine arm versus 3m5 months in the control arm (Prince HM et al. 2017).

Undesirable effectsThis section has been translated automatically.

The treatment-related side effects with Brentuximab Vedotine were mainly of severity 1 (minor side effects) or 2 (general condition worsened, chemotherapeutic agent must be reduced) in all studies. Side effects of severity 3 (interruption of chemotherapy necessary) or 4 (hospitalisation required) were caused by cytopenia (mainly neutropenia). The most frequent side effects of WHO severity grades 3 or 4 in the pivotal Hodgkin lymphoma study (102 patients) were: neutropenia 20%, peripheral neuropathy 9%, thrombocytopenia 8%, anemia 6% (Younes A et al. 2012).

Neuropathies usually regressed over time (Pro B et al 2012). However, in the pivotal trial for cutaneous T-cell lymphomas 24% of patients had to discontinue treatment for peripheral neuropathies (Siegmund-Schultze N 2018). Further described are cases of progressive multifocal leukoencephalopathy (PML).

PreparationsThis section has been translated automatically.

Adcetris®

LiteratureThis section has been translated automatically.

  1. Prince HM et al (2017) Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet 390:555-566.
  2. Pro B et al (2012) Brentuximab Vedotin (SGN-35) in Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma: Results of a Phase II Study. J Clin Oncol 30: 2190-2196
  3. Senter PD et al (2012) The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Nat Biotechnol 30: 631-637
  4. Siegmund-Schultze N (2018) Cutaneous T-cell lxmphomas. Dtsch Ärztebl 115: 765
  5. Younes A et al (2012) Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma. J Clin Oncol 30: 2183-2189

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Last updated on: 29.10.2020