Brentuximab vedotin

Overview

Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL. The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seagen in the US.[1][2] WP

Uses, dosage and effects

Medical uses

In the United States, brentuximab vedotin is indicated for the treatment of Hodgkin lymphoma, systemic anaplastic large cell lymphoma, primary cutaneous anaplastic large cell lymphoma, and CD30-expressing mycosis fungoides.[3] WP

In the European Union, brentuximab vedotin is indicated for the treatment of Hodgkin lymphoma, systemic anaplastic large cell lymphoma, and cutaneous T cell lymphoma.[4] WP

Research

Clinical trials

In a 2010, clinical trial, 34% of patients with refractory Hodgkin lymphoma achieved complete remission and another 40% had partial remission. Tumor reductions were achieved in 94% of patients. In ALCL, 87% of patients had tumors shrink at least 50% and 97% of patients had some tumor shrinkage.[5][6][7] WP

Reports in 2013, showed interim results from a Phase II, open-label, single-arm study designed to evaluate the antitumor activity of brentuximab vedotin in relapsed or refractory CD30-positive NHL, including B-cell neoplasms. These results demonstrated that single-agent brentuximab vedotin induced a 42% objective response rate and manageable safety profile among advanced diffuse large B-cell lymphoma patients.[8][9][10] WP

A phase III trial funded by Millennium Pharmaceuticals compared ABVD (a combination of the chemotherapy drugs doxorubicin, bleomycin, vinblastine, and dacarbazine) versus A+AVD (a combination of brentuximab vedotin plus AVD, or doxorubicin, vinblastine, and dacarbazine) for treatment of classical Hodgkin lymphoma and found substituting brentuximab vedotin for bleomycin has both improved efficacy and lowered toxicity. A previously completed phase I study demonstrated that a greater number of patients experienced pulmonary toxicity with brentuximab vedotin-ABVD than with ABVD alone. Pulmonary fibrosis is a classical adverse effect of bleomycin; however, the incidence of pulmonary fibrosis in the brentuximab vedotin-ABVD arm was higher than the expected historical rate with ABVD alone. Overall, 24 out of 25 patients treated with brentuximab vedotin and AVD achieved complete remission.[11][12][13] WP

Brentuximab vedotin is also being investigated as a substitute for vincristine (another mitotic inhibitor which prevents tubulin polymerization) in patients with being treated with CHOP (a combination of cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone or prednisolone) for a non-Hodgkin lymphoma. WP

A phase III clinical trial comparing the two combination therapies (CHOP and CHP-brentuximab vedotin) was completed in October 2020, with results published in 2021.[14][15] WP

The ECHELON-1 phase 3 trial compared brentuximab vedotin with bleomycin both in combination with adriamycin, vinblastine, dacarbazine (AVD) chemotherapy as a firstline treatment for advanced classical Hodgkin lymphoma. The outcome of the trial resulted in a positive recommendation by the Committee for Medicinal Products for Human Use (CHMP) as part of a combination treatment in adults with previously untreated CD30+ stage 3 Hodgkin lymphoma.[16][17] WP

Legal status

Legal status

In August 2011, the US Food and Drug Administration (FDA) granted accelerated approval to the biologics license application (BLA) submitted by Seattle Genetics for the use of brentuximab vedotin in the treatment of relapsed HL and ALCL.[18][19] WP

In October 2012, the European Medicines Agency (EMA) gave it conditional marketing authorization for relapsed or refractory HL and ALCL.[4][20] WP

In November 2017, the FDA approved brentuximab vedotin as a treatment for patients with cutaneous T-cell lymphoma (CTCL) who have received prior systemic therapy. This approval is for patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF).[21] WP

In March 2018, the FDA approved brentuximab vedotin to treat adults with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy.[22][23] WP

In November 2018, the FDA expanded the approved use of brentuximab vedotin in combination with chemotherapy for adults with certain types of peripheral T-cell lymphoma (PTCL). This is the first FDA approval for treatment of newly diagnosed PTCL.[24] WP

In November 2022, the FDA approved brentuximab vedotin in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide for people aged two years of age and older with previously untreated high risk classical Hodgkin lymphoma. This is the first pediatric approval for brentuximab vedotin.[25] WP

Economics

The Australian Pharmaceutical Benefits Advisory Committee (PBAC) considered a March 2014 application by the manufacturer for inclusion of brentuximab vedotin under a Pharmaceutical Benefits Scheme Section 100 (Efficient Funding of Chemotherapy) arrangement. While this application was accepted, the committee noted that on the basis of inadequate cost-benefit, the medicine would not be made available more generally for the first-line treatment of relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).[26] WP

Brand names

Brentuximab vedotin is marketed as Adcetris.[27] WP

Chemistry

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Seattle Genetics Submits BLA to FDA for brentuximab vedotin in relapsed or refractory hodgkin lymphoma and systemic ALCL. 28 February 2011
2. Other Takeda and Millennium Announce Approval of Adcetris (Brentuximab Vedotin) in Switzerland
3. Journal / agency Adcetris- brentuximab vedotin injection, powder, lyophilized, for solution. 26 November 2018
4. Journal / agency Adcetris EPAR. 17 September 2018
5. Other ClinicalTrialsGov NCT00848926 A Pivotal Open-Label Trial of Brentuximab Vedotin for Hodgkin Lymphoma
6. Other at 2010 Annual Meeting of the American Society of Hematology (ASH) (Corporate Press Release) Deprecated archive
7. Other Is Seattle Genetics the Next Big Thing?. 2 December 2010
8. Journal / agency Maeda T, Wakasawa T, Shima Y, Tsuboi I, Aizawa S, Tamai I. Role of polyamines derived from arginine in differentiation and proliferation of human blood cells. Biological & Pharmaceutical Bulletin. February 2006. doi:10.1182/blood.V122.21.848.848 · PMID 16462024
9. Other ClinicalTrialsGov NCT01421667 A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma
10. Journal / agency Brentuximab Vedotin Shows 42% Objective Response Rate in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma, Study Shows. ADC Review / Journal of Antibody-drug Conjugates. 10 December 2013
11. Journal / agency Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. The New England Journal of Medicine. January 2018. doi:10.1056/NEJMoa1708984 · PMID 29224502 · PMC5819601
12. Journal / agency FDA Drug Safety Communication: New Boxed Warning and Contraindication for Adcetris (brentuximab vedotin). 13 January 2012
13. Journal / agency Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. The Lancet. Oncology. December 2013. doi:10.1016/S1470-2045(13)70501-1 · PMID 24239220
14. Other ClinicalTrialsGov NCT01777152 A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in the Frontline Treatment of Patients With CD30-positive Mature T-cell Lymphomas
15. Journal / agency Horwitz S, O'Connor OA, Pro B, Trümper L, Iyer S, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Menne T, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Zinzani PL, Miao H, Bunn V, Fenton K, Fanale M, Puhlmann M, Illidge T. The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma. Annals of Oncology. March 2022. doi:10.1016/j.annonc.2021.12.002 · PMID 34921960 · PMC9447792
16. Other Pagliarulo N. Seattle Genetics' Adcetris succeeds in study but shares slide. June 2017
17. Other Takeda announces CHMP recommendation for Adcetris in Hodgkin lymphoma. 21 September 2023
18. Journal / agency Brentuximab Vedotin (marketed as Adcetris) Information. 3 November 2018
19. Other Seattle Genetics' Antibody-Drug Conjugate Receives FDA Okay to Treat Lymphomas. 22 August 2011
20. Journal / agency EMA/European Medicines Agency: EPAR summary for the public for Adcetris/brentuximab vedotin. link 2
21. Other FDA Approves Brentuximab Vedotin for CTCL. 2017
22. Journal / agency FDA expands approval of Adcetris for first-line treatment of Stage III or IV classical Hodgkin lymphoma in combination with chemotherapy. 20 March 2018
23. Journal / agency brentuximab vedotin. 20 March 2018
24. Journal / agency FDA approves first-line treatment for peripheral T-cell lymphoma under new review pilot. 16 November 2018
25. Journal / agency FDA approves brentuximab vedotin in combination with chemotherapy for pediatric patients with classical Hodgkin lymphoma. 10 November 2022
26. Other Brentuximab Vedotin, 50 mg injection, 1 x 50 mg vial Adcetris. March 2014
27. Other Hofland P. European Medicines Agency Accepts Brentuximab Marketing Authorization Application. 27 June 2011

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