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.
DEXAPOMA+ISAT
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 relapsed or refractory multiple myeloma (MM) in patients with good performance status, who have received at least 2 previous lines of treatment (including lenalidomide and a proteasome inhibitor).
(Refer to NDFP form for details)
dexamethasone
ODB - General Benefit
(dexamethasone)
isatuximab
New Drug Funding Program
(Isatuximab - In Combination with Pomalidomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma)
(NDFP Website
)
pomalidomide
Exceptional Access Program
(pomalidomide - In combination with isatuximab and dexamethasone for relapsed or refractory multiple myeloma, according to specific criteria)
(EAP Website)
Cycle 1:
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dexamethasone † | 40* mg | IV / PO | Days 1, 8, 15, and 22 |
| isatuximab | 10 mg /kg | IV | Days 1, 8, 15, and 22 |
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pomalidomide ^ | 4 mg | PO daily | Days 1 to 21 |
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dexamethasone † | 40* mg | IV / PO | Days 1, 8, 15, and 22 |
| isatuximab | 10 mg /kg | IV | Days 1 and 15 |
|
pomalidomide ^ | 4 mg | PO daily | Days 1 to 21 |
†Give before isatuximab on isatuximab infusion days (also refer to premedication section).
*Decrease dexamethasone dose to 20 mg in patients > 75 years old.
^Pomalidomide 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.
Low
No routine prophylaxis for pomalidomide
- 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:
- Isatuximab can interfere with cross-matching for blood transfusions; type and screen and RBC genotyping tests should be done before starting this drug.
- Consider antiviral prophylaxis for herpes zoster reactivation.
- Prophylactic antithrombotics, such as low dose aspirin, low molecular weight heparins or warfarin, are recommended.
- Patients at risk of tumour lysis syndrome should have appropriate prophylaxis and be monitored closely.
Pre-medications (prophylaxis for infusion reaction):
To be given 15-60 minutes prior to infusion:
- Dexamethasone 40 mg IV/PO*
- Acetaminophen 650-1000 mg PO (or equivalent)
- Diphenhydramine 25-50 mg IV/PO (or equivalent)†
- H2 antagonist
*Dexamethasone is part of combination therapy; the treatment dose will serve as pre-medication on infusion days. Additional corticosteroids are not required as pre-medication on infusion days when dexamethasone is given. Decrease dexamethasone dose to 20 mg in patients ≥ 75 years old.
†IV preferred for at least the first 4 infusions.
Doses should be modified according to the protocol by which the patient is being treated.
Pomalidomide 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.
People of child bearing potential must have two negative pregnancy tests before initiating treatment.
Start treatment only if ANC ≥ 1 x 109/L and platelets ≥ 50 x 109/L.
Dosage with toxicity
Dose Levels:
| Dose Level | Pomalidomide Dose (mg/day) | Dexamethasone Dose (mg/day) | |
| 0 | 4 | 40 | 20* |
| -1 | 3 | 20 | 12 |
| -2 | 2 | 12 | 8 |
| -3 | 1 | 8 | 4 |
| -4 | Discontinue | 4 | Discontinue |
| -5 | N/A | Discontinue | N/A |
*Starting dose for patients ≥ 75 years old.
Dose reductions are not recommended for isatuximab. Doses may be delayed or discontinued in case of neutropenia or IRs.
Dexamethasone doses may be held or reduced for dexamethasone-related adverse events (i.e. hypertension, hyperglycemia, fluid retention) to improve tolerability.
Hematological toxicity
| Toxicity | Action | |
| Pomalidomide | Isatuximab | |
| Grade 3 Neutropenia (ANC 0.5 to < 1 x 109/L) |
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Grade 4 neutropenia OR Febrile neutropenia |
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| Grade 4 thrombocytopenia (platelets < 25 x 109/L) |
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*Do not re-start until ANC returns to ≥ 1 x 109/L and platelets ≥ 50 x 109/L, and non-hematological toxicities resolve to ≤ grade 2.
Non-hematological toxicity
|
Toxicity |
Dose of Pomalidomide* |
| Grade 2 or 3 skin rash | Hold or discontinue. Resume if benefit outweighs potential risk. |
| Grade 4 rash or rash with exfoliation, bullae or purpura, angioedema, anaphylaxis, or suspected SJS/TEN/DRESS | Discontinue. |
| Grade 3 or 4 non-hematologic/organ toxicities | Hold until recovery* then ↓ 1 dose level. Consider discontinuing if grade 4. |
| Acute onset or worsening of pulmonary symptoms | Hold and investigate for pneumonitis. Resume only after an evaluation of the benefits and risks. |
| PML | Hold and investigate. Discontinue if confirmed. |
*Do not re-start until ANC returns to ≥ 1 x 109/L and platelets ≥ 50 x 109/L, and non-hematological toxicities resolve to ≤ grade 2.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge |
| 1 |
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| 2 |
Restart:
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| 3 or 4 |
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*Give diphenhydramine 25 mg IV (or equivalent) and/or methylprednisolone 100 mg IV (or equivalent) and/or epinephrine (for Gr. 3-4) as needed to manage symptoms.
Hepatic Impairment
Pomalidomide is primarily metabolized in the liver. Hepatic impairment results in a 51-72% increase in drug exposure. The starting dose of pomalidomide should be adjusted as follows:
| Hepatic Impairment | Pomalidomide Dose* (mg/day) |
Isatuximab Dose** |
| Mild | 3 | No dose adjustment necessary |
| Moderate | 3 | No data |
| Severe | 2 |
Renal Impairment
No dose adjustment for isatuximab is recommended in patients with renal impairment.
Pomalidomide and its metabolites are renally excreted. Pomalidomide is dialysable. The starting dose of pomalidomide should be adjusted for severe impairment requiring dialysis, as follows:
| Creatinine Clearance (mL/min) |
Pomalidomide Starting Dose (mg/day) |
| < 30 requiring dialysis | 3 (taken after dialysis) |
Dosage in the Elderly
The starting dose of dexamethasone should be reduced to 20 mg in patients > 75 years. No dose adjustments for pomalidomide or isatuximab are recommended based on age.
When pomalidomide was given in combination with dexamethasone, patients > 65 years were observed to have higher incidences of infection and pneumonia than younger patients.
No overall safety or efficacy differences were observed between younger and older patients given isatuximab.
Refer to isatuximab, pomalidomide drug monograph(s) for additional details of adverse effects.
|
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
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Refer to isatuximab, pomalidomide drug monograph(s) for additional details.
- Avoid strong inhibitors of CYP1A2 if possible. If not possible to avoid, reduce the pomalidomide dose by 50%.
- Avoid CYP1A2 inducers if possible; cigarette smoking may reduce the efficacy of pomalidomide.
- Pomalidomide increases thromboembolic risk and would have an additive effect if co-administered with other thromboembolic agents. Hormonal contraceptives are not recommended due to the increased risk of thromboembolism.
- Isatuximab interferes with the indirect antiglobulin (Coombs) test by binding to CD38 on RBCs. Patient's blood should be typed and screened, and RBC genotyped prior to initiating treatment. Notify blood transfusion centres of this in the event of a planned transfusion and educate patients.
- Isatuximab 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 isatuximab, pomalidomide drug monograph(s) for additional details.
Administration: Pomalidomide
Pomalidomide 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.
- Capsule should be swallowed whole with a glass of water. Do not crush or open the capsule.
- Doses may be administered with or without food.
- Missed dose: If less than 12 hours has passed since the missed dose, the dose may be taken. If more than 12 hours has passed since the missed dose, skip this dose and take the next one at its usual time the next day. Do not give a double dose to make up for a missed one.
- On dialysis days, administer pomalidomide after the completion of hemodialysis due to possible significant decrease in drug exposure.
- People who could become pregnant or who plan to become pregnant can handle pomalidomide capsules if they are using latex gloves.
- Store at room temperature (15-30°C) in original package in order to protect from light.
Administration: Isatuximab
- Refer to Infusion Rate table below.
- Dilute with 250 mL of NS or D5W.
- The infusion bag must be made of polyolefins (PO), polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) with di (2-ethylhexyl) phthalate (DEHP) or ethyl vinyl acetate (EVA).
- Mix by gently inverting the bag. Do not shake.
- Administer by IV infusion using an IV tubing infusion set (in polyethylene [PE], polyvinyl chloride [PVC] with or without di (2-ethylhexyl) phthalate [DEHP], polybutadiene [PBD] or polyurethane [PU]) with an in-line filter (polyethersulfone [PES], polysulfone or nylon).
- Do not infuse concomitantly in the same IV line with other agents.
- Store unopened vials between 2 to 8°C (36°F to 46°F). Protect from light.
Infusion Rate
Isatuximab should be administered at the initial infusion rate with incremental escalation as described below. Infusion rate escalations should only be considered in the absence of infusion-related reactions (IRs).
| Dilution Volume |
Initial Rate | Absence of IRs | Rate Escalation | Maximum Rate | |
| 1st Infusion | 250 mL | 25 mL/hr | For 60 min | 25 mL/hr q30 min | 150 mL/hr |
| 2nd Infusion | 250 mL | 50 mL/hr | For 30 min |
50 mL/hr for 30 min, |
200 mL/hr |
| Subsequent Infusions |
250 mL | 200 mL/hr | - | - | 200 mL/hr |
Contraindications
- Patients who have a hypersensitivity to isatuximab, dexamethasone, pomalidomide, or any of their components, or to thalidomide or lenalidomide.
- Patients who are pregnant, at risk of becoming pregnant, or are breastfeeding (Refer to Pregnancy and Lactation section)
- People unable to comply with required contraceptive measures
Warnings/Precautions
- Patients with primary refractory disease or who progressed or were refractory to anti-CD38 treatment were excluded from isatuximab clinical trials.
- Avoid use of pomalidomide in patients with active / history of hepatitis A, B, or C.
- Avoid use of pomalidomide in patients taking other immunosuppressive treatments, to reduce the risk of developing serious infections.
- Patients should not donate blood or semen while taking pomalidomide, during treatment interruptions, and for 4 weeks after treatment cessation.
- Use with caution and consider prophylaxis when pomalidomide is used in combination with corticosteroids or thrombogenic agents, such as hormones and erythropoietin or in patients with risk factors for arterial or venous thromboembolism (e.g. hypertension, hyperlipidemia, previous history of thromboembolism, or taking other agents that increase thromboembolic risk).
- Use pomalidomide with caution in patients with pre-existing ≥ grade 2 neuropathy.
- Use with caution when operating machinery, or when driving, as confusion, fatigue, depressed level of consciousness and dizziness may occur with treatment.
- Use with caution in patients with significant cardiac dysfunction (i.e. CHF NYHA Class III or IV, MI within 12 months, unstable or poorly controlled angina) as pomalidomide use has not been studied in these patients. Atrial fibrillation has occurred, especially in patients with pre-existing cardiac disease or cardiac risk factors.
Pregnancy/Lactation
- This regimen is contraindicated for use in pregnancy and in people who do not comply with the contraception conditions of pomalidomide's controlled distribution program. Refer to the controlled distribution program for full details.
- Adequate contraception should be used by patients and their partners while on therapy and after treatment is completed. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
- Breastfeeding is contraindicated during this treatment. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
- Fertility effects:
- Pomalidomide: Probable
- Isatuximab: Unknown
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
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CBC; Baseline, weekly for the first 8 weeks then before each cycle
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Blood type and screen, and RBC genotype; Before starting isatuximab. In the event of a planned transfusion, notify blood transfusion centres.
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Liver function tests; Baseline and before each cycle
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Electrolytes, renal function tests; Baseline and before each cycle
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Controlled distribution program requirements regarding pregnancy tests for women of child-bearing potential; Before starting, during treatment and for at least 4 weeks after discontinuation
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Clinical toxicity assessment for infusion-related reactions, infection (including viral reactivation), bleeding, hypersensitivity, thromboembolism, secondary malignancies, pneumonitis, hepatitis, TLS, neurological, GI, cardiac, and skin effects; 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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DEXAPOMA: Outpatient prescription for home administration
Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107.
CADTH Reimbursement Recommendation: Isatuximab (Sarclisa). Canadian Journal of Health Technologies. February 2022.
DEXAPOMA regimen monograph, Ontario Health (Cancer Care Ontario).
Isatuximab drug monograph. Ontario Health (Cancer Care Ontario).
Pomalidomide drug monograph. Ontario Health (Cancer Care Ontario).
San Miguel J et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM- 003): a randomized, open-label, phase 3 trial. Lancet Oncol 2013;14:1055-66.
February 2024 Expanded to full regimen monograph
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.