Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
DARA(MNT-SC)
Multiple Myeloma
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.
- As maintenance (after completion of combination treatment*) in patients with newly diagnosed (transplant ineligible) or relapsed multiple myeloma, who have good performance status
- As maintenance after completion of CYBORD in patients with light chain (AL) amyloidosis, who have good performance status
*Refer to NDFP forms in Supplementary Public Funding section for details on funded regimens.
daratumumab (subcut)
New Drug Funding Program
(Daratumumab in Combination with a Bortezomib-Based Regimen for Newly Diagnosed Transplant Ineligible Multiple Myeloma)
(NDFP Website
)
daratumumab (subcut)
New Drug Funding Program
(Daratumumab - In Combination with Bortezomib and Dexamethasone for Relapsed Multiple Myeloma)
(NDFP Website
)
daratumumab (subcut)
New Drug Funding Program
(Daratumumab and Bortezomib in combo with Cyclophosphamide and Dexamethasone - Previously Untreated Light Chain (AL) Amyloidosis)
(NDFP Website
)
Note: Different daratumumab products are NOT INTERCHANGEABLE.
As maintenance treatment (after completion of daratumumab combination* therapy):
| daratumumab (subcut) | 1800 mg | Subcut | Day 1 |
*Refer to NDFP forms for details on funded regimens.
REPEAT EVERY 28 DAYS
Multiple myeloma: Until disease progression or unacceptable toxicity.
Light chain amyloidosis: Up to 24 cycles of treatment (including CYBORD+DARA(SC) cycles) or until disease progression or unacceptable toxicity, whichever occurs first
Minimal
Other Supportive Care:
- Also refer to CCO Antiemetic Recommendations.
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HBV screening should be performed in all patients prior to starting daratumumab.
-
Consider antiviral prophylaxis for herpes zoster reactivation.
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Daratumumab can interfere with cross-matching for blood transfusions; type and screen and RBC genotyping tests should be done before starting this drug.
Pre-medications for daratumumab (subcut) monotherapy (prophylaxis for administration-related reactions (ARRs)):
To be given at least 1 hour prior to each dose:
- Corticosteroid IV/PO (e.g., methylprednisolone 100 mg or equivalent)*
- Oral antipyretic (e.g., acetaminophen 650-1000 mg)
- H1-receptor antagonist IV/PO (e.g., diphenhydramine 25-50 mg or equivalent)
- Montelukast 10 mg PO‡
*This dose may be reduced after the 2nd injection (e.g., methylprednisolone 60 mg IV or equivalent).
‡Montelukast 10 mg was optional on Cycle 1 Day 1 during clinical trials of daratumumab (subcut). The addition of montelukast given prior to the first daratumumab IV infusion numerically reduced the incidence of respiratory IRs in the study by Nooka et al.
Post-injection medications for daratumumab (subcut) monotherapy (prevention of delayed ARRs):
- Oral corticosteroid (e.g., methylprednisolone 20 mg or equivalent) for 2 days post-injection§
- Consider bronchodilators (e.g., short and long acting) and inhaled corticosteroids (for patients with a history of COPD)#
§These may be discontinued after the 3rd injection if no major systemic ARRs occurred.
#These may be discontinued after the 4th injection if no major ARRs occurred.
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
Dose Levels: No dose reductions of daratumumab (subcut) are recommended. Dose delays may be required.
| Toxicity | Grade/Severity | Action |
|---|---|---|
| Neutropenia | Grade 4 |
Hold until < Grade 2. Consider use of colony-stimulating factors (e.g., G-CSF). |
| Thrombocytopenia | Grade 3 or 4 |
Hold until < Grade 2. |
| Hepatitis B virus (HBV) reactivation |
Hold daratumumab, concomitant steroids and chemotherapy. Consult with an HBV expert and manage appropriately. Restart of daratumumab treatment in patients whose HBV reactivation is adequately controlled should be discussed with physicians with expertise in managing HBV. |
Management of Administration-Related Reactions (ARRs):
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
| Hepatic Impairment | Daratumumab (Subcut) Dose |
| Mild (total bilirubin 1 to 1.5 times ULN or AST > ULN) | No dose adjustment necessary. |
| Moderate (total bilirubin >1.5 to 3 times ULN and any AST) | Limited data. |
| Severe (total bilirubin >3 times ULN and any AST) |
Renal Impairment
No dosage adjustment is necessary for patients with renal impairment.
Dosage in the Elderly
No dose adjustment is required in patients ≥ 65 years of age. No overall differences in efficacy were observed but patients ≥ 65 years were more likely to experience serious adverse events (e.g., pneumonia) than those < 65 years.
Refer to daratumumab (subcut) drug monograph(s) for additional details of adverse effects.
The incidences below were mostly reported for daratumumab IV. Adverse events associated with the subcutaneous formulation are denoted with “^”.
|
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
Refer to daratumumab (subcut) drug monograph(s) for additional details.
- Daratumumab interferes with the indirect antiglobulin (Coombs) test by binding to CD38 on RBCs. Daratumumab-mediated positive Coombs test may persist for up to 6 months after treatment completion. Patient's blood should be typed and screened prior to initiating treatment. Notify blood transfusion centres of this in the event of a planned transfusion and educate patients.
- Daratumumab may interfere with the serum protein electrophoreses (SPE) and immunofixation (IFE) assays used to monitor M-protein. This can impact the monitoring of response and disease progression in some patients with IgG kappa myeloma protein.
Refer to daratumumab (subcut) drug monograph(s) for additional details.
Administration:
Daratumumab IV and subcutaneous formulations are not interchangeable. The dosing and administration of these products are different.
- Daratumumab (subcut) does not require reconstitution or dilution.
- Compatible with polypropylene or polyethylene syringe material, polypropylene, polyethylene, or polyvinyl chloride (PVC) subcutaneous infusion sets, and stainless steel transfer and injection needles.
- Administer by subcutaneous injection, over approximately 3-5 minutes.
- Inject into the abdominal wall only (approximately 7.5 cm to the right or left of the navel). Do not give in areas where the skin is red, bruised, tender, hard or where there are scars.
- If pain occurs during injection, pause or slow rate of injection. If pain is not improved, the remaining dose may be given at an alternate injection site (on the opposite side of the abdomen).
- If there are other subcutaneous medications, they should be given at separate sites.
- Do not shake vials.
- Store vials at 2-8°C. Bring vials to room temperature (15-30°C) before use. Keep out of direct sunlight.
Contraindications:
- Patients who have a hypersensitivity to this drug or any of its components
Warnings/Precautions:
- Daratumumab can cause severe administration-related reactions (ARRs), including anaphylaxis. It should only be administered by healthcare professionals with appropriate medical support to manage these reactions. Pre- and post-injection medications should be administered. Refer to Dosing section.
- Daratumumab (subcut) is not recommended for use in patients with AL amyloidosis with advanced cardiac disease.
Pregnancy/Lactation:
- Daratumumab (subcut) should not be used in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 3 months after the last dose.
- Breastfeeding is not recommended.
- Fertility Effects: Unknown
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 before each dose
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Blood; Type and screen prior to initiation. In the event of a planned transfusion, notify blood transfusion centres.
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Electrolytes, renal function tests; Baseline and as clinically indicated
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Liver function tests; Baseline and as clinically indicated
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Immunoglobulin levels; Baseline and as clinically indicated
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HBV serology; Baseline for all patients and as clinically indicated. For patients with evidence of HBV serology at baseline, monitor during treatment and for at least 6 months post treatment. Consult with an expert in HBV.
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Clinical toxicity assessment for systemic administration-related reactions, injection-site reactions, hypersensitivity, infection, bleeding, anemia, cardiac, and GI effects; Baseline and at each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Daratumumab drug monograph, Ontario Health (Cancer Care Ontario).
Daratumumab (subcut) drug monograph, Ontario Health (Cancer Care Ontario).
Mateos MV, Nahi H, Legiec W, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020 May;7(5):e370-e380.
Mateos MV, Cavo M, Blade J, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet 2020 Jan 11;395(10218):132-41.
Nooka AK, Gleason C, Sargeant MO, et al. Managing infusion reactions to new monoclonal antibodies in multiple myeloma: daratumumab and elotuzumab. J Oncol Pract 2018 Jul;14(7):414-22.
Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385(1):46-58.
Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Aug 25;375(8):754-66.
pCODR Expert review committee final recommendation: Daratumumab for the treatment of patients with newly diagnosed multiple myeloma. Aug 29, 2019.
Yimer H, Melear J, Edward Faber E, et al. Lyra: a phase 2 study of daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (Cybord) in newly diagnosed and relapsed patients (Pts) with multiple myeloma. Blood 2018;132 (Supplement 1):152.
September 2022 Added NDFP forms; modified Rationale and uses, and Cycle frequency 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.