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.
BORTDEXALENA
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 the treatment of patients with previously untreated multiple myeloma, who have good performance status
(Note: Patients who do not meet the LU eligibility criteria for lenalidomide may apply for case-by-case consideration through the EAP.)
bortezomib
New Drug Funding Program
(Bortezomib - In Combination with Lenalidomide and Dexamethasone for Previously Untreated Multiple Myeloma Pre-SCT)
(NDFP Website
)
bortezomib
New Drug Funding Program
(Bortezomib - In Combination with Lenalidomide and Dexamethasone for Previously Untreated Multiple Myeloma Without Intent for Stem Cell Transplantation)
(NDFP Website
)
lenalidomide
ODB Limited Use
(lenalidomide - Induction therapy for transplant eligible, newly diagnosed multiple myeloma, according to clinical criteria)
(ODB Formulary
)
lenalidomide
ODB Limited Use
(lenalidomide - For the treatment of patients with multiple myeloma, who are deemed to be lenalidomide sensitive, and/or have not experienced progression while on a lenalidomide-based regimen in the treatment or maintenance setting, according to clinical criteria)
(ODB Formulary
)
dexamethasone
ODB - General Benefit
(dexamethasone)
(ODB Formulary)
| bortezomib | 1.3 to 1.5 mg /m² | IV / Subcut | Days 1, 8, 15 |
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| lenalidomide | 10 to 25 mg | PO | Days 1 to 14 |
| dexamethasone | 40* mg | PO | Days 1, 8 and 15 |
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Note: Different doses and/or dosing schedules have been used in clinical trials. Careful consideration of risk vs. benefit, the published literature and the protocol being used is required prior to finalizing the doses to be used for individual patients.
Lenalidomide may only be prescribed and dispensed by physicians and pharmacists registered with a controlled distribution program. Patients must also be registered and meet all conditions of the program.
REPEAT EVERY 21 DAYS
Transplant ineligible patients:
For up to 8 cycles unless disease progression or unacceptable toxicity occurs
Starting with cycle 9 onwards, continue with lenalidomide (at dose tolerated at the end of cycle 8) and dexamethasone (DEXALENA*) as maintenance until disease progression or unacceptable toxicity.
(*Refer to schedule in Durie et al)
Transplant eligible patients:
Give up to 4 cycles and assess for response and suitability for transplant.
Low
No routine prophylaxis for lenalidomide
- Also refer to CCO Antiemetic Recommendations.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Other Supportive Care:
-
Antiviral prophylaxis for herpes zoster is recommended.
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Patients at risk of tumour lysis syndrome should have appropriate prophylaxis and be monitored closely.
-
Prophylaxis for venous thromboembolism is recommended in patients at risk (e.g. low dose aspirin 81-100 mg PO daily or enoxaparin 40 mg SC daily).
-
Careful consideration and monitoring must be taken with erythropoietin stimulating agents (ESAs), since the concomitant use of ESAs with lenalidomide may potentiate the risk of thrombosis. RBC or platelet transfusions with lenalidomide dose reductions/interruptions may be appropriate in severe / symptomatic anemia or thrombocytopenia.
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Consider GCSF as secondary prophylaxis.
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Optimal control of thyroid function is recommended prior to starting treatment.
Doses should be modified according to the protocol by which the patient is being treated.
Women of child bearing potential must have two negative pregnancy tests before initiating treatment.
Dosage with toxicity
Dose levels
| Dose level | Bortezomib (mg/m2) | Lenalidomide (mg) | Dexamethasone (mg) |
| 0 | 1.3 | 25 | 40 |
| -1 | 1 | 15 | 20 |
| -2 | 0.7 | 10 | 12 |
| -3 | Discontinue if further reduction indicated | 5 | Discontinue if further reduction indicated |
| -4 | Not applicable | Discontinue | Not applicable |
Hematologic toxicity*
|
Toxicity during cycle (counts x 109/L) |
Bortezomib** |
Lenalidomide** |
|
1st instance: platelets < 30 |
Consider hold until platelets ≥ 30, then resume at 1 dose level reduction |
Hold until platelets ≥ 30, then resume at 1 dose level reduction
|
|
Subsequent instances: platelets < 30 |
Consider hold until platelets ≥ 30, then resume at 1 dose level reduction |
Hold until platelets ≥ 30, then resume at 1 additional dose level reduction |
|
1st instance: ANC < 0.75 |
Hold until ANC ≥ 1, then resume at the same dose |
Hold until ANC ≥ 1, add G-CSF if possible, then resume at the same dose if isolated neutropenia. Reduce dose by 1 dose level if other toxicity. |
|
Subsequent instances: ANC < 0.75 |
Hold until ANC ≥ 1, then resume at 1 dose level reduction |
Hold until ANC ≥ 1, add G-CSF if possible, then resume at 1 dose level reduction |
|
Toxicity |
Bortezomib |
Lenalidomide |
Dexamethasone |
|
Grade 2 fluid retention |
Reduce one dose level |
n/a |
Consider dose reduction |
|
Grade 3 or 4 fluid retention |
Discontinue |
n/a |
Consider dose reduction |
| Grade 2 to 3 rash | For drug related grade 3: Hold until ≤ grade 1 or baseline, then resume at 1 dose level reduction. If recurs, reduce an additional dose level | Hold or consider discontinuing | N/A |
|
Angioedema, anaphylaxis, OR Suspected Stevens Johnson Syndrome, Toxic epidermal necrolysis or DRESS |
Discontinue |
||
|
Pneumonitis |
Hold and investigate; discontinue if confirmed. |
n/a |
|
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PRES / PML |
Hold and investigate; discontinue if confirmed. |
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Increased LFTs |
n/a |
Hold until ≤ baseline. Consider restarting at a lower dose. |
n/a |
| Solid organ transplant rejection | Discontinue | ||
|
Any ≤ grade 3 non-heme toxicity (for neurotoxicity with bortezomib, see separate table below) |
Hold until ≤ grade 1 or baseline, then resume at 1 dose level reduction. If recurs, reduce an additional dose level. For grade 4 toxicity, consider discontinuation. |
Hold until ≤ grade 1 or baseline, then resume at 1 dose level reduction. If recurs, reduce an additional dose level. |
Hold until ≤ grade 1 or baseline, then resume at 1 dose level reduction. If recurs, reduce an additional dose level. |
Dosage for neurotoxicity
Patients with pre-existing severe neuropathy should be treated with bortezomib only after careful risk vs. benefit assessment.
|
Severity of Neuropathy |
Bortezomib dosage |
|
Grade 1 (paresthesias, weakness and/or loss of reflexes) without pain or loss of function |
No change |
|
Grade 1 with pain or Grade 2 (interfering with function but not with activities of daily living) |
Reduce 1 dose level |
|
Grade 2 with pain or Grade 3 (interfering with activities of daily living) |
Hold until toxicity resolves. Upon recovery, resume at 1 additional dose level reduction and give once weekly. |
|
Grade 4 (sensory neuropathy which is disabling or motor neuropathy that is life-threatening or leads to paralysis) and/or severe autonomic neuropathy |
Discontinue permanently |
Hepatic Impairment
Bortezomib is metabolized by liver enzymes and exposure is increased in patients with moderate to severe hepatic impairment.
|
Bilirubin |
|
AST |
Bortezomib starting dose |
Lenalidomide starting dose | Dexamethasone starting dose |
|
≤ 1 x ULN |
and |
> ULN |
No change |
No change | No change |
|
> 1 – 1.5 x ULN |
and |
Any |
No change |
No change | No change |
|
> 1.5 x ULN |
and |
Any |
1st cycle: ↓ to 0.7 mg/m2 Subsequent cycles: Consider ↑ dose to 1 mg/m2 OR further ↓ dose to 0.5 mg/m2 based on patient tolerability |
No data | No change |
Renal Impairment
Lenalidomide clearance is decreased while exposure is increased in renal impairment.
|
Creatinine Clearance (mL/min) |
Lenalidomide Starting Dose |
Bortezomib starting dose |
Dexamethasone starting dose |
|
30 to < 60 |
10 mg daily* |
No change |
No change |
|
< 30 (not requiring dialysis) |
15 mg every other day |
No change; monitor carefully |
No change |
|
< 30 (requiring dialysis) |
No phase III clinical trial experience in this setting. 5 mg once daily. On dialysis days, administer following dialysis |
No change. On dialysis days, administer following dialysis |
No change |
Dosage in the Elderly
The incidences of serious and non-serious adverse events are significantly higher in patients > 65 years with lenalidomide and this may be related to renal impairment. Monitor elderly patients closely, especially cardiac and renal function. Dose modification based on degree of renal impairment is required.
No dosage adjustment is required for bortezomib or dexamethasone.
Refer to bortezomib, lenalidomide, dexamethasone drug monograph(s) for additional details of adverse effects.
|
Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
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Refer to bortezomib, lenalidomide, dexamethasone drug monograph(s) for additional details
- Avoid bortezomib co-administration with strong CYP3A4 inhibitors and inducers.
- Avoid use of bortezomib with high dose cytarabine or daunorubicin given increased risk of ARDS.
- Avoid green tea and preparations containing green tea during bortezomib treatment .
- Avoid vitamin C supplementation during bortezomib treatment.
- Caution and monitor with drugs associated with neuropathy, hypoglycemia and hypotension.
- Caution and consider non-hormonal method(s) of contraception; use of oral contraceptives or other hormonal methods of contraception may increase the risk of blood clots.
- Lenalidomide increases the concentration of digoxin. Use caution and monitor digoxin levels.
- Lenalidomide increases the risk of thromboembolism, and can have an additive effect with hormonal therapy, erythropoietic agents, and corticosteroids.
Refer to bortezomib, lenalidomide, dexamethasone drug monograph(s) for additional details
Administration
Bortezomib:
- Bortezomib should be administered via intravenous or subcutaneous routes only.
- Bortezomib is fatal if given intrathecally.
- Bortezomib has a narrow therapeutic range. If a different reconstituted concentration is used for each route of administration, exercise caution when reconstituting and calculating the dose volume.
- The Canadian product monograph recommends the following concentrations to be used for injections: ► Intravenous: 1 mg/mL; ► Subcutaneous: 2.5 mg/mL
- If local injection site reactions occur following subcutaneous bortezomib, consider using a less concentrated solution subcutaneously (1 mg/mL), or administer as IV.
- IV: Administered as a 3 to 5 second IV push through a peripheral or central IV catheter, followed by a standard saline flush; no central line is required.
- For subcutaneous use, bortezomib solution is injected into the right or left sides of the thighs or abdomen. Rotate injection sites with subsequent injections. Give new injections at least 2.5 cm from an old site and never into areas where the site is tender, bruised, erythematous, or indurated.
Lenalidomide:
- Drug available by outpatient prescription in pharmacy registered with a controlled distribution program.
- Oral self-administration; swallow capsules whole; they should not be broken, chewed, or opened. Do not extensively handle the capsules.
- Give capsules preferably with water, either with or without food. Do not remove from blister packs until ready to take the dose.
Note: Females who could become pregnant, or who plan to become pregnant can handle lenalidomide capsules if they are using latex gloves. - If a dose is missed, it may be taken up to 12 hours after the time it is normally taken. Otherwise, skip this and take the next dose on the following day at its usual scheduled time.
- Store capsules at room temperature (15 to 30°C).
Dexamethasone:
- oral self-administration
- give tablets with food, preferably in the morning
Contraindications
- Patients with hypersensitivity to bortezomib, boron, mannitol, lenalidomide, pomalidomide, thalidomide or any ingredient in the formulation
- Bortezomib is NOT for intrathecal use
- Pregnant and breastfeeding women
- Women at risk of being pregnant and male patients who do not comply with contraception requirements (see Pregnancy section in lenalidomide drug monograph for additional details)
Other warnings/precautions
- Lenalidomide contains lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption
- Use with caution and consider venous thromboembolism prophylaxis when used in combination with corticosteroids or thrombogenic agents, such as hormones and erythropoietin (see adverse effects section)
- Exercise caution in patients with risk factors for arterial thromboembolism (e.g. hypertension and hyperlipidemia), or risk factors for atrial fibrillation (e.g. electrolyte abnormalities, pre-existing heart disease, hypertension, infection).
- Use with caution in patients with high tumour burden; monitor closely and use appropriate precautions for tumour lysis syndrome.
- Use with caution and monitor closely in patients with previous viral infections such as HBV and herpes zoster.
- Caution should be exercised when driving or using machinery, and in patients on medication(s) that may lead to hypotension, or patients with dehydration or history of syncope, due to the risk of hypotension and dizziness.
- Use with caution in patients with amyloidosis, those with risk factors for seizures, cardiac disease, pre-existing neuropathies
Pregnancy & Lactation
- Lenalidomide is contraindicated in pregnancy and in females and males of childbearing potential who do not comply with the contraception conditions of the controlled distribution program.
- Bortezomib is not recommended for use during pregnancy.
- Breastfeeding is contraindicated.
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
-
CBC; baseline and before each cycle
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Blood glucose levels, especially in patients using antidiabetic medications; baseline, before each cycle and as clinically indicated
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Liver and renal function tests; Baseline and before each cycle
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CXR; baseline, then CXR and lung function assessment if ILD is suspected
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Thyroid function tests; Baseline and as clinically indicated
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Specific to lenalidomide: Pregnancy testing requirements for women of child-bearing potential; prior to starting treatment and as indicated
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Cancer screening for occurrence of second primary malignancy; assess risk prior to starting treatment, then at each visit or as clinically indicated
-
Clinical toxicity ratings of fatigue, neurotoxicity, infection (including viral reactivation), bleeding, rash, diarrhea, constipation, arterial and venous thromboembolism, respiratory symptoms, tumour lysis syndrome, cardiovascular and GI side effects, GVHD and organ transplant rejection (if applicable); at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
-
EKG at baseline; repeat if arrhythmia suspected
-
LVEF monitoring in patients with cardiac risk factors; baseline and as clinically indicated
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INR in patients receiving warfarin; baseline and regular
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Outpatient prescription for home administration (lenalidomide & dexamethasone)
Attal M, Lauwers-Cances V, Hulin C, et al, Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med 2017;376(14):1311-20.
Bortezomib drug monograph. Ontario Health (Cancer Care Ontario).
Durie BGM, Hoering A, Sexton R, et al, Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT). Blood Cancer J 2020;10(5):53.
Durie BGM, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 2017 Feb 4;389(10068):519-27.
Lenalidomide drug monograph. Ontario Health (Cancer Care Ontario).
Richardson PG, Xie W, Jagannath S, et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood 2014 Mar 6;123(10):1461-9.
Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010 Aug 5;116(5):679-86.
December 2023 Modified Supplementary public funding and Drug regimen sections
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.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, 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.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.