You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search
A - Regimen Name

CARF Regimen
Carfilzomib


Disease Site
Hematologic - Multiple Myeloma

Intent
Palliative

Regimen Category
Evidence-Informed :

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.


Rationale and Uses

For the treatment of relapsed or refractory multiple myeloma in patients who have received two or more prior therapies for relapsed disease.

 
B - Drug Regimen

Cycle 1:

carfilzomib
20 mg /m² IV Days 1, 2, 8, 9, 15, 16
(This drug is not currently publicly funded for this regimen and intent)

 

Cycles 2-12:

carfilzomib

1

27 mg /m² IV Days 1, 2, 8, 9, 15, 16
(This drug is not currently publicly funded for this regimen and intent)

1 If cycle 1 at the initial dose level of 20 mg/m2 was well tolerated, the dose was escalated to 27 mg/m2 for all subsequent cycles

back to top
 
C - Cycle Frequency

REPEAT EVERY 28 DAYS

Until disease progression or unacceptable toxicity.

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Low

Other Supportive Care:

Also refer to CCO Antiemetic Summary

Carfilzomib:

  • Consider the use of antiviral prophylaxis during carfilzomib therapy to decrease the risk of herpes zoster reactivation.

  • Thromboprophylaxis is recommended in patients being treated with carfilzomib in combination with dexamethasone. The choice of agent should be based on patient risk factors and clinical status.

  • Hypertension should be well-controlled prior to initiation of treatment with carfilzomib.

  • Adequate hydration is required prior to dosing in cycle 1, especially in patients at high risk for tumour lysis syndrome or renal toxicity. The total fluid volume may be adjusted as clinically indicated in patients with baseline or at high risk of cardiac failure.

  • Cycle 1:

    • oral fluids (30 mL/kg/day for 48 hours before start of cycle)

    • 250-500 mL of IV fluid before and after each dose (if needed)

  • Subsequent cycles:

    • continue oral and/or IV hydration as needed

  • Dexamethasone IV/PO should be given at least 30 minutes, but no more than 4 hours before carfilzomib.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated.

Patients with BSA > 2.2 m2 should be dosed based on a maximum BSA of 2.2 m2. Dose adjustments for carfilzomib do not need to be made for weight changes ≤ 20%.

Refer to carfilzomib drug monograph for additional details on dose modifications.

Dosage with toxicity

Dose levels

Dose level

Carfilzomib (mg/m2)

0

27

-1

20

-2

15

-3

Discontinue

 

Dose Modifications for Hematological and Non-Hematological Toxicities:

Toxicity

Carfilzomib Dose

Hematologic

ANC < 0.5 x 109/L, febrile neutropenia or platelets < 10 x 109/L ; thrombocytopenic bleeding

1st instance: hold until recovery* (and/or bleeding is controlled, fever resolves), and then restart at the same dose level.

Subsequent instances: hold until recovery* (and/or bleeding is controlled); consider restarting at 1 dose level ↓.

Increased creatinine

SCr ≥ 2 x baseline, or CrCl < 15 mL/min (or CrCl decreases to ≤ 50% of baseline) or need for dialysis

Hold:

  • If attributable to carfilzomib, resume at 1 dose level ↓ when renal function has recovered to within 25% of baseline.

  • If not attributable to carfilzomib, may resume at physician's discretion.

If tolerated, the reduced dose may be increased to the previous dose.

Grade 3 or 4 cardiac events

Hold until resolved. Consider risk vs. benefit of restarting; resume at 1 dose level ↓.

Hypertensive crisis/emergency

Hold until resolves or under control.

Consider the risk vs. benefit of restarting; consider restarting at 1 dose level ↓.

ARDS, ILD, pneumonitis, pulmonary hypertension, grade 3 or 4 dyspnea Hold until resolves. Consider the risk vs. benefit of restarting.
Thrombotic microangiopathy (including TTP/HUS) Hold and evaluate. Discontinue if confirmed.
PRES Hold and evaluate. Discontinue if confirmed.
All other Grade 3 or 4 non-hematological toxicities Hold until resolved or at baseline. After resolution, if appropriate to reinitiate, consider restarting at 1 dose level ↓.

*Do not retreat until ANC ≥ 0.5 x 109/L (or baseline values for febrile neutropenia) and platelets ≥ 10 x 109/L with resolution of fever and bleeding



Hepatic Impairment

In a pharmacokinetic study, carfilzomib AUC increased by 50% in patients with baseline mild or moderate hepatic impairment compared to those with normal hepatic function. The incidence of serious adverse events was higher in patients with hepatic impairment as well.

Impairment

Carfilzomib Starting Dose

Mild ( bilirubin > 1-1.5 x ULN or AST > ULN) or moderate (bilirubin > 1.5-3 x ULN)

Reduce dose by 25%

Severe (bilirubin > 3 x ULN)

No data


Renal Impairment

No dose adjustment is required for carfilzomib in patients with baseline renal impairment. For patients on dialysis receiving carfilzomib, administer dose after dialysis.


Dosage in the Elderly

There was a higher incidence of certain adverse effects (including cardiac failure) observed in patients ≥ 65 years of age, especially those more than 75 years, when carfilzomib was given in combination with lenalidomide and dexamethasone.


 
F - Adverse Effects

Refer to carfilzomib 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

  • Infusion related reaction (maybe severe)
  • Diarrhea (maybe severe)
  • Hypertension
  • Fatigue
  • Fever
  • Cough, dyspnea
  • Myelosuppression ± infection, bleeding
  • Insomnia
  • Edema
  • Nausea, vomiting
  • Musculoskeletal pain, weakness
  • Headache
  • Constipation
  • Peripheral neuropathy
  • Abnormal electrolyte(s)(K, Ca, PO4, Mg)
  • Hyperglycemia
  • Abdominal pain
  • Creatinine increased
  • Cardiotoxicity
  • Venous thromboembolism
  • Arterial thromboembolism
  • Adult respiratory distress syndrome (ARDS)
  • Pneumonitis
  • Pulmonary hypertension
  • Cataract
  • Tumor lysis syndrome (rare)
  • GI perforation (rare)
  • Thrombotic microangiopathy (rare) (includes TTP, HUS)
  • RPLS / PRES
 
G - Interactions

Refer to carfilzomib drug monograph(s) for additional details


  • It is unknown whether carfilzomib is an inducer of CYP1A2, 2C8, 2C9, 2C19 and 2B6. Caution should be observed when combined with products which are substrates of these enzymes, including oral contraceptives.

  • Carfilzomib does not induce, but may inhibit, CYP3A4/5.

  • Caution with P-glycoprotein substrates (i.e. verapamil, digoxin, morphine, ondansetron) and monitor digoxin levels.

  • Caution and consider non-hormonal method(s) of contraception as use of oral contraceptives or other hormonal methods of contraception may have reduced efficacy and may increase the risk of blood clots.

 
H - Drug Administration and Special Precautions

Refer to carfilzomib drug monograph(s) for additional details


Administration:

  • Carfilzomib should be given as a 10 minute infusion
  • May further dilute dose in 50-100 mL D5W. Do not dilute in NS for IV administration.

  • Carfilzomib should not be administered as an IV bolus. Maybe administered directly by IV infusion or in an IV bag.

  • Flush line before and after carfilzomib administration with NS or D5W.

  • After reconstitution, gently swirl and/or invert the vial slowly for 1 minute. Do not shake.

  • If foaming occurs, allow the solution to settle in the vial until foaming subsides (approximately 5 minutes) and the solution is clear, colourless and free of visible particulates.

  • Stable in D5W. Do not mix with or administer as an infusion with other medications.

  • The time from reconstitution to administration should not exceed 24 hours.

  • Unreconstituted carfilzomib powder for injection should be stored in unopened vials at 2–8°C.

 

Contraindications:

  • Patients who have a hypersensitivity to these drugs or any of their components
     

Other Warnings/Precautions:

  • Use carfilzomib with caution in patients on a controlled sodium diet. Each mL contains 0.3 mmols (7 mg) of sodium.

  • The risk of heart failure is increased in elderly patients (≥ 75 years).  Patients with NYHA Class III/IV heart failure, recent MI, conduction abnormalities, angina or arrhythmias uncontrolled by medications were not eligible for carfilzomib-based clinical trials.  These patients may be at greater risk of cardiac complications and should have their medical management optimized, including hypertension, prior to starting treatment with carfilzomib and monitored closely throughout.

  • Use caution with driving or using machinery as fatigue, dizziness and a drop in blood pressure may occur with carfilzomib treatment.

 

Pregnancy and Lactation:

  • Carfilzomib is not recommended for use in pregnancy.

    • Adequate contraception should be used by female patients and/or their male partners during carfilzomib treatment, and for 30 days after the last dose.

    • Adequate contraception should be used by male patients and/or their female partners during carfilzomib treatment, and for 90 days after the last dose.

  • Breastfeeding is not recommended .

  • Fertility effects: no information available.

 
I - Recommended Clinical Monitoring

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

  • Blood pressure; Baseline and before each treatment

  • CBC with differential; Baseline and before each treatment week

  • Electrolytes, including potassium; Baseline and before each cycle

  • Liver function tests; Baseline and before each cycle

  • Renal function tests; Baseline and before each cycle

  • Clinical toxicity assessment for GI, skin, respiratory, cardiovascular  and neurological effects as well as infusion reactions, bleeding, infection, tumour lysis and venous or arterial thromboembolism; At each visit

  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

  • Blood glucose levels; Baseline and regular

  • ECG; Baseline; repeat if arrhythmia suspected

  • LVEF assessment (especially in patients ≥ 75 years, or those at greater risk for cardiac complications); Baseline and as clinically indicated


back to top
 
J - Administrative Information

Approximate Patient Visit
First cycle: 9 hours (includes pre-IV hydration); Cycles 2 to 12: 3 hours (if no IV hydration)
Pharmacy Workload (average time per visit)
19.850 minutes
Nursing Workload (average time per visit)
42.417 minutes
 
K - References

Carfilzomib drug monograph, Cancer Care Ontario.

Kyprolis (carfilzomib) [prescribing information]. Thousand Oaks, CA: Onyx Pharmaceuticals Inc; June 2018.

Siegel DS, Martin T, Wang M, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood 2012;120:2817-25.


June 2019 added PEBC guideline link


back to top
 
M - Disclaimer

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.