Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
BREN(CONS)
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
For consolidation treatment in Hodgkin lymphoma patients with risk factors for relapse or progression* post-autologous stem cell transplant (ASCT).
*Patients with increased risk of relapse or progression as defined in the pivotal trial:
- Refractory to frontline therapy or;
- Relapsed less than 12 months from frontline therapy or;
- Relapse 12 months or greater after frontline therapy with extranodal disease.
brentuximab vedotin
New Drug Funding Program
(Brentuximab Vedotin - Consolidation Post-Autologous Stem Cell Transplant (ASCT) for Hodgkin Lymphoma)
|
brentuximab vedotin * | 1.8 mg /kg | IV | Day 1 |
*Start treatment within 4 to 6 weeks post-ASCT or upon recovery from ASCT. Maximum dose 180 mg for patients who are ≥ 100 kg.
REPEAT EVERY 21 DAYS
For up to 16 cycles unless disease progression or unacceptable toxicity occurs
Refer to NDFP form for details on brentuximab vedotin funding in a subsequent line of therapy.
Low
Low
Premedication (Prophylaxis for Infusion Reactions):
- Routine pre-medication is not recommended.
- May consider pre-medication with acetaminophen, H1-receptor antagonist and corticosteroid if an IR has occurred in the past.
Other supportive care:
- Antiviral and antibiotic prophylaxis post-ASCT should be followed per institutional guidelines.
- Patients at risk of tumour lysis syndrome should have appropriate prophylaxis and be monitored closely.
- Also refer to CCO Antiemetic Recommendations.
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
|
Toxicity |
Type / Grade |
Brentuximab vedotin dose |
|
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Peripheral neuropathy
|
New or worsening Grade 2 or 3 |
Hold until improvement to Grade 1 or baseline, then restart at 1.2 mg/kg.^ |
|
|
Grade 4 |
Discontinue. |
||
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Neutropenia
|
Grade 3 or 4 |
Hold until ≤ Grade 2. Consider growth factor support for subsequent cycles. |
|
|
Recurrent Grade 4 despite the use of growth factors |
Consider discontinuing, or reduce dose to 1.2 mg/kg when recovered to ≤ Grade 2.^ |
||
| Thrombocytopenia | Grade 3 or 4 | Monitor closely and consider platelet transfusions or dose delays. | |
|
SJS, TEN |
Any |
Discontinue and manage appropriately. |
|
|
PML |
Suspected, any grade |
Hold and investigate; discontinue if confirmed. |
|
| Pancreatitis | Suspected, any grade | Hold and investigate; discontinue if confirmed. | |
| Pulmonary symptoms | Any grade | Hold and investigate; consider discontinuing if pneumonitis confirmed. | |
|
Tumour lysis syndrome |
Suspected, any grade |
Hold and manage aggressively. May continue therapy after resolution with adequate preventative measures. |
|
| Hepatotoxicity | New, worsening or recurrent | Hold and consider reduced dose. Discontinue if severe. | |
^Maximum dose: 120 mg (for 1.2mg/kg dose) in patients ≥ 100 kg.
Management of Infusion-Related Reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge |
| 1 or 2 |
Restart:
|
|
| 3 |
Restart:
|
|
| 4 |
|
|
Hepatic Impairment
The liver is a known route of clearance for brentuximab vedotin. MMAE exposure approximately doubled in patients with hepatic impairment; a reduced starting dose should be used.
| Hepatic Impairment | Dose |
| Mild (Child-Pugh A) | Start at 1.2 mg/kg† and monitor closely. |
| Moderate (Child-Pugh B) | Avoid use. |
| Severe (Child-Pugh C) | Avoid use. |
†Maximum dose: 120 mg (for 1.2 mg/kg dose) in patients ≥ 100 kg.
Renal Impairment
No dose adjustment for mild or moderate renal impairment. Avoid use in patients with severe renal impairment (CrCl <30mL/min). The kidneys are a known route of clearance for brentuximab vedotin. MMAE exposure approximately doubled and severe adverse effects were more frequent in patients with severe renal impairment.
Dosage in the Elderly
No specific dose adjustment is recommended by the manufacturer.
Efficacy and safety of monotherapy have not been established in geriatric patients with HL at high risk of relapse, or relapsed/refractory HL.
Older age was a risk factor for febrile neutropenia for brentuximab in combination with chemotherapy.
Refer to brentuximab vedotin drug monograph(s) for additional details of adverse effects.
|
Very common (≥ 50%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
Refer to brentuximab vedotin drug monograph(s) for additional details.
- Concomitant use of bleomycin is contraindicated given increased risk of pulmonary toxicity.
Refer to brentuximab vedotin drug monograph(s) for additional details
Administration
- DO NOT administer as an IV push or bolus.
- Reconstitute based on product monograph instructions to yield a single-use 5 mg/mL solution.
- After reconstitution, immediately add to an infusion bag containing at least 100 mL volume to achieve a final concentration of 0.4-1.8 mg/mL.
- Can be diluted into normal saline, 5% dextrose or lactated Ringer's injection.
- Infuse IV over 30 minutes.
- Do not mix with, or administer as an infusion with, other medicinal products.
- Store unopened vials at 2-8°C in the original carton to protect from light.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications
- Patients who are hypersensitive to this drug or any of its components
- Concomitant use with bleomycin due to increased risk of pulmonary toxicity
- Patients who have, or have had progressive multifocal leukoencephalopathy (PML)
Warnings/Precautions
- Patients with significant pre-existing cardiovascular disease should be monitored closely as the potential cardiotoxicity of brentuximab vedotin is unknown.
- Use live vaccines with caution.
Pregnancy/Lactation
- Brentuximab is not recommended for use in pregnancy unless possible benefits to the mother outweigh risks to the fetus. Adequate contraception (including a barrier method) should be used by both sexes during treatment, and for at least 6 months after the last dose.
- Breastfeeding is not recommended.
- Effects in fertility: Documented in animals
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Recommended Clinical Monitoring
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CBC; Baseline and prior to each dose; more frequent monitoring should be considered for patients with Grade 3 or 4 neutropenia or thrombocytopenia
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Liver function tests; Baseline and before each cycle, also as clinically indicated in patients with liver impairment
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Renal function tests; Baseline and before each cycle, also as clinically indicated in patients with renal impairment
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Clinical toxicity assessment for TLS, PML, infusion-related reactions, infections, bleeding, neuropathy, pneumonitis, pancreatitis, thromboembolism, GI or skin effects, fatigue, pain; At each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Blood glucose; Baseline and as clinically indicated, especially for patients with a history of diabetes mellitus
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Brentuximab vedotin drug monograph, Ontario Health (Cancer Care Ontario).
Moskowitz CH, Nademanee A, Masszi T, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015;2015: 1853-62.
December 2021 Added details on brentuximab vedotin funding to Cycle frequency section
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
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