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The ADC that made the modern field credible (2011), for Hodgkin lymphoma and CD30+ lymphomas.
Brentuximab vedotin is a chimeric anti-CD30 IgG1 antibody carrying the microtubule poison MMAE (drug-to-antibody ratio about 4) through a cleavable mc-vc-PABC linker; inside a CD30-positive cell MMAE blocks mitosis and diffuses to kill neighbouring cells. Approved in 2011 for relapsed Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, it made the modern ADC field credible and later moved to first line with AVD (ECHELON-1, overall survival benefit), CD30-positive peripheral T-cell lymphoma with CHP (ECHELON-2), post-transplant consolidation (AETHERA) and paediatric Hodgkin lymphoma. Peripheral neuropathy affected 65 percent of the A+AVD arm in ECHELON-1 and neutropenia 91 percent, so G-CSF prophylaxis is mandatory and bleomycin is contraindicated. Its vc-MMAE linker-payload was reused in enfortumab, polatuzumab, tisotumab and disitamab vedotin.
Ball-and-stick model from PubChem 2D record (no 3D conformer available). PubChem record
Chimeric anti-CD30 IgG1 with MMAE.
1.Antibody binds CD30 on the tumour cell surface
Source: US prescribing information (DailyMed). Doses are for orientation; the current label governs.
Given by infusion or injection in a clinic or hospital outpatient department, so it is a Part B drug: Medicare pays 80% after the Part B deductible and the patient owes 20% coinsurance, uncapped in Original Medicare unless a Medigap policy applies. HCPCS J9042.
Covered under the medical benefit with prior authorisation confirming diagnosis, biomarker status and line of therapy; site-of-care policies may steer infusions away from hospital outpatient departments.
20% Part B coinsurance on a high-cost infusion adds up quickly: Medigap Plan G or N, Medicare Advantage maximum out-of-pocket, Medicaid dual eligibility, or a charity fund are the usual buffers.
Sources: Medicare.gov: Chemotherapy · Medicare.gov: Prescription drugs (outpatient, Part B). Not medical or financial advice; verify with your plan.
Sources: NICE TA446 · SMC advice: brentuximab vedotin. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
| Date | Deal | Type | Upfront | Total | Source |
|---|---|---|---|---|---|
| 2023-03-13 | Seagen to Pfizer (incl. Seagen) Padcev, Tivdak, Adcetris, Tukysa and the vedotin ADC platform | Acquisition | not disclosed | $43bn | source |
Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT), or after failure of at least 2 multi-agent chemotherapy regimens in patients who are not ASCT candidates
Accelerated approval, relapsed Hodgkin lymphoma and systemic ALCL source
Systemic anaplastic large cell lymphoma after failure of at least one multi-agent chemotherapy regimen
Accelerated approval on a surrogate endpoint, with a confirmatory trial required.
Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT), or after failure of at least 2 multi-agent chemotherapy regimens in patients who are not ASCT candidates
Post-transplant consolidation in Hodgkin lymphoma (AETHERA) source
Systemic anaplastic large cell lymphoma after failure of at least one multi-agent chemotherapy regimen
First-line stage III/IV Hodgkin lymphoma with AVD (ECHELON-1) source
First-line CD30+ peripheral T-cell lymphoma with CHP (ECHELON-2) source
Paediatric high-risk Hodgkin lymphoma source
| Region | Year | Indication |
|---|---|---|
| US | 2011 | Relapsed Hodgkin lymphoma and systemic ALCL |
| US | 2018 | First-line stage III/IV Hodgkin lymphoma with AVD |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Neutropenia | 91% | 82% |
| Peripheral sensory neuropathy | 65% | 10% |
| Constipation | 42% | 2% |
| Nausea | 40% | 2% |
| Vomiting | 33% | 3% |
| Febrile neutropenia | 19% | 19% |
ECHELON-1, A+AVD arm. Rates read from the US prescribing information. Blank cells mean the figure was not sourced, not that it is zero.
Read for the class this product belongs to (antibody-drug conjugates with an mmae payload) unless the answer names the product. Population figures from the cohorts named, not a prediction for one person. Blank where no source gives a recovery figure.
| Country | Reimbursement | List price | Assistance |
|---|---|---|---|
| United States | Medicare Part B (physician-administered); commercial plans per formulary | not disclosed | - |
| United Kingdom | NICE: recommended in CD30+ Hodgkin lymphoma settings (TA446, TA524) and first-line stage IV with AVD | not disclosed | - |
List prices are manufacturer or Medicare figures where publicly disclosed; net prices after rebates are usually lower. Reimbursement changes; check the payer.
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The evidence behind the United States approval of brentuximab vedotin with lenalidomide and a rituximab product for relapsed or refractory diffuse large B-cell lymphoma after two or more lines in patients not eligible for an autologous transplant or CAR-T. It is also the first demonstration that a CD30-directed conjugate helps in a disease where CD30 expression is variable.
For fit younger patients treated in the intensive German tradition, BrECADD replaces escalated BEACOPP; how it compares with nivolumab-AVD from S1826 is the open question.
S1826 moved checkpoint blockade into first-line Hodgkin lymphoma and made N-AVD a preferred regimen for advanced disease in patients from adolescence to older age, while removing radiotherapy for most. It also showed the value of a single trial spanning paediatric and adult groups. Longer follow-up is needed for overall survival and late immune effects in young patients.
Brentuximab vedotin with AVEPC is the new standard for high-risk paediatric Hodgkin lymphoma and led to the first paediatric approval of the drug in November 2022.
PD-1 blockade is the standard for classical Hodgkin lymphoma that has relapsed after or is unsuitable for autologous transplant, ahead of brentuximab vedotin in most patients.
ECHELON-1 made a targeted antibody-drug conjugate part of first-line Hodgkin therapy and eventually showed that this saves lives, not just relapses. It set the reference arm against which nivolumab-AVD (SWOG S1826) and BrECADD (HD21) were later compared. Neuropathy is the main price and needs proactive dose modification.
Brentuximab vedotin is a standard for CD30-positive cutaneous T-cell lymphoma requiring systemic therapy, including large cell transformation.
Patients at high risk of relapse after autologous transplant are offered brentuximab vedotin consolidation; the benefit is largest in those with two or more risk factors.
Query for this drug: (TITLE:"Brentuximab vedotin" OR ABSTRACT:"Brentuximab vedotin" OR TITLE:"Adcetris" OR ABSTRACT:"Adcetris") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Brentuximab vedotin, not a curated reading list.
Shares Breast implant-associated anaplastic large cell lymphoma, B-cell, T-cell and NK-cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma.
Shares Caution: bleomycin lung toxicity, especially with brentuximab or G-CSF, AHOD2131 (COG / NCTN), Chemotherapy-free Hodgkin lymphoma: brentuximab + PD-1 in early stage, GHSG HD21.
Shares Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Mycosis fungoides, Relapsed and refractory classical Hodgkin lymphoma.
Shares GHSG HD21: PET-guided BrECADD versus escalated BEACOPP in advanced-stage classical Hodgkin lymphoma, Peter Borchmann, German Hodgkin Study Group, GHSG HD21.
Shares Peter Borchmann, German Hodgkin Study Group, A radiotherapy-free cure for early Hodgkin lymphoma that actually holds, RADAR.
Shares Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Sezary syndrome, Relapsed and refractory classical Hodgkin lymphoma, Early-stage classical Hodgkin lymphoma (stage I to II).
Shares Peter Borchmann, German Hodgkin Study Group, A radiotherapy-free cure for early Hodgkin lymphoma that actually holds, RADAR.
Shares Peter Borchmann, German Hodgkin Study Group, Primary cutaneous anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma.