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.
CYBORD+DARA(SC)
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.
This 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). 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.
Treatment of newly diagnosed light-chain amyloidosis.
bortezomib
New Drug Funding Program
(Daratumumab and Bortezomib in combo with Cyclophosphamide and Dexamethasone - Previously Untreated Light Chain (AL) Amyloidosis)
(NDFP Website
)
dexamethasone
ODB - General Benefit
(dexamethasone)
(ODB Formulary
)
daratumumab (subcut)
New Drug Funding Program
(Daratumumab and Bortezomib in combo with Cyclophosphamide and Dexamethasone - Previously Untreated Light Chain (AL) Amyloidosis)
(NDFP Website
)
cyclophosphamide
ODB - General Benefit
(cyclophosphamide - oral tablets)
Note: Different daratumumab products are NOT INTERCHANGEABLE
Cycles 1 and 2:
| daratumumab (subcut) | 1800 mg | Subcut | Days 1, 8, 15, 22 |
|
cyclophosphamide † | 300 mg /m² | PO (max 500 mg) | Days 1, 8, 15, 22 |
|
bortezomib † | 1.3 mg /m² | Subcut | Days 1, 8, 15, 22 |
|
dexamethasone ^ | 40 mg | PO | Days 1, 8, 15, 22 |
|
Cycles 3 to 6: |
|||
| daratumumab (subcut) | 1800 mg | Subcut | Days 1 and 15 |
|
cyclophosphamide † | 300 mg /m² | PO (max 500 mg) | Days 1, 8, 15, 22 |
|
bortezomib † | 1.3 mg /m² | Subcut | Days 1, 8, 15, 22 |
|
dexamethasone ^ | 40 mg | PO | Days 1, 8, 15, 22 |
|
See DARA(MNT-SC) for Cycles 7 and beyond
|
|||
† Missed doses should not be made up. For bortezomib, there should be a minimum of 72 h between doses.
^The dexamethasone dose should be reduced in elderly patients.
REPEAT EVERY 28 DAYS
For up to 6 cycles, unless disease progression or unacceptable toxicity
Refer to DARA(MNT-SC) for CYCLES 7+ (after CYBORD is completed) for daratumumab maintenance.
Low
Consider prophylaxis daily for cyclophosphamide PO
Also refer to CCO Antiemetic Recommendations.
Supportive care:
-
HBV screening should be performed in all patients prior to starting daratumumab.
-
Consider antiviral prophylaxis for herpes zoster reactivation.
- Daratumumab can interfere with cross-matching for blood transfusions; type and screen and RBC genotyping tests should be done before starting this drug.
-
Patients at risk of tumour lysis syndrome should have appropriate prophylaxis and be monitored closely.
-
Oral hydration is encouraged to prevent dose-related hemorrhagic cystitis.
-
Prophylaxis with a proton pump inhibitor and an antibiotic (e.g. quinolone) were also used in some clinical trials.
-
Use of anti-fungal mouthwash was recommended in some clinical trials.
Pre-medications for Daratumumab (subcut) (prophylaxis for administration-related reactions (ARRs)):
To be given at least 1 hour prior to each dose:
- Dexamethasone 20 mg IV/PO †
- 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‡
†Dexamethasone on the day of injection may be given as part of pre-/post-medications for daratumumab; 20 mg IV/PO on the day of daratumumab injection and 20 mg PO on the day after injection. For patients receiving reduced dose dexamethasone 20 mg weekly, the entire 20 mg dose has been given prior to the daratumumab injection in some clinical trials.
‡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 infusion reactions in the study by Nooka et al.
Post-Injection Medications for Daratumumab (subcut) (prevention of delayed ARRs):
- Dexamethasone 20 mg PO for 1 day post-injection¶,§
- Consider bronchodilators (e.g., short and long acting) and inhaled corticosteroids (for patients with a history of COPD) || #
¶Dexamethasone on the day of injection may be given as part of pre-/post-medications for daratumumab; 20 mg IV/PO on the day of daratumumab injection and 20 mg PO on the day after injection. For patients receiving reduced dose dexamethasone 20 mg weekly, the entire 20 mg dose has been given prior to the daratumumab injection in some clinical trials.
§May be discontinued after the 3rd injection if no major systemic ARRs occurred (excluding regimen-specific corticosteroids).
||Consider adding an H1-receptor antagonist if the patient is at higher risk of respiratory complications.
#May be discontinued after the 4th injection if no major ARRs occurred.
Cyclophosphamide and Dexamethasone: Outpatient prescription for home administration
Bortezomib and cyclophosphamide drug monographs, Cancer Care Ontario.
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.
Palladini G, Kastritis E, Maurer MS, et al. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA.Blood. 2020;136(1):71-80.
September 2022 Added NDFP form (bortezomib and daratumumab); modified Rationale/uses, Drug regimen 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.