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Treatment Name: CRD (Carfilzomib + Revlimid® + Dexametha­sone)

CRD (Carfilzomib + Revlimid® + Dexametha­sone) is a Chemotherapy Regimen for Multiple Myeloma (MM)

How does CRD work?
Each of the medications in the CRD or KRD chemotherapy regimen is designed to kill or slow the growth of myeloma cells.

C – Carfilzomib (Kyprolis®)
R - Revlimid® (lenalidomide)
D - Dexamethasone (Deltasone, dex)

or

K - Kyprolis® (carfilzomib)
R - Revlimid® (lenalidomide)
D - Dexamethasone (Deltasone, dex)

Goals of therapy:
CRD or KRD is given to alleviate symptoms and slow the progression of multiple myeloma, not for cure of disease. After treatment, patients who respond to CRD may be monitored in clinic with periodic blood tests, continue with maintenance therapy, or proceed to bone marrow transplant.

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Schedule

  • Carfilzomib intravenous (I.V.) infusion over 10 minutes,
    • on Days 1, 2, 8, 9, 15 & 16 of Cycles 1 - 12
    • on Days 1, 2, 15 & 16 of Cycles 13 - 18 (no Day 8 or 9)
  • Lenalidomide 25 mg capsule by mouth once daily on Days 1 through 21
  • Dexamethasone 40 mg (ten 4 mg tablets) by mouth on Days 1, 8, 15, and 22 of each cycle

Lenalidomide is a human teratogen. In order to decrease the risk of embryo-fetal exposure, lenalidomide is available only through a restricted distribution program (Revlimid® REMS).

Carfilzomib is usually given in an outpatient infusion center, allowing the person to go home afterwards. Lenalidomide and dexamathasone are usually taken at home.

CRD is repeated every 28 days. This is known as one Cycle. Each cycle may be repeated up to 8 times, depending upon the stage of the disease. Duration of therapy may last up to eight months, depending upon response, tolerability, and number of cycles prescribed.

Click here for Common CRd doses.

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Side Effects

In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported side effects with CRD are shown here. Side effects sometimes have percentage ranges [example: 33 – 38% had fatigue] because they differed between clinical studies:

  • High blood sugar (72%)
  • Increased bleeding risk [low platelets] (68%)
  • Anemia [low red blood cells] (60%)
  • Fluid accumulation (47%)
  • Fatigue (33 - 38%)
  • Low white blood cells (30%)
  • Cough (29%)
  • Fever (29%)
  • Sinus infection (29%)
  • Low potassium (29%)
  • Rash (28%)
  • Muscle spasm or cramps (27 - 32%)
  • Diarrhea (26 - 42%)
  • Tingling in fingers and toes (23%)
  • Trouble breathing (15 - 19%)
  • High blood pressure (14%)
  • Blood clots (11%)
  • Constipation (9%)
  • Kidney injury (8%)
  • Clots in lungs (6%)

On average, 15% of patients discontinue CRD due to unacceptable side effects.

Side effect videos Side Effect Videos
Fatigue Fatigue DiarrheaDiarrheaConstipationConstipationPainPain

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Monitoring

How often is monitoring needed?
Labs (blood tests) may be checked before treatment and periodically during treatment. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), plus any others your doctor may order.

How often is imaging needed?
Imaging may be checked before treatment and then periodically during treatment to assess how the chemotherapy is working. Imaging may include: bone surveys, computerized tomography (CT) scans, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans.

How might blood test results affect treatment?
Depending upon the results, your doctor may advise to continue chemotherapy as planned, or delay or switch therapy.

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ChemoExperts Tips

  • Hydration (salt water or "saline" infusion) before and after carfilzomib can help prevent kidney toxicity
  • Some infusion centers may infuse carfilzomib over 30 minutes to help decrease infusion reactions
  • Some infusion centers give patients two carfilzomib doses in one day instead of one dose on two consecutive days
  • Side effects are relatively common with this regimen. A dosage reduction in lenalidomide (Revlimid) may be required in certain individuals in order to decrease the frequency or severity of side effects
  • Additional medications that may be prescribed include Bactrim® (Sulfamethoxazole/Trimethoprim) to prevent Pneumocystis Pneumonia, and omeprazole (or a similar medication) to prevent ulcers from dexamethasone
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for myeloma. Ask your doctor if any studies are currently enrolling in your area or go to clinicaltrials.gov and search “myeloma” to find other centers offering study medications

Patient Assistance & Co-payment Coverage

Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for CRD (Carfilzomib + Revlimid® + Dexametha­sone), we have provided links that may help.

Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for CRD (Carfilzomib + Revlimid® + Dexametha­sone). Depending upon your income, they may be able to help cover the cost of:

  • Carfilzomib
  • Revlimid®
  • Dexamethasone

For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.

  • If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.

Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as CRD (Carfilzomib + Revlimid® + Dexametha­sone) and are the best source to help you understand drug cost.

  • Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.

Emotional Wellness

What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.

Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.

Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.

Learn more about pursuing emotional wellness while receiving treatment with CRD (Carfilzomib + Revlimid® + Dexametha­sone)

Individual Drug Label Information

Carfilzomib (Kyprolis®)

  • Carfilzomib is an intravenous (I.V.) injection infused over two to ten minutes
  • If you miss a scheduled dose, your physician will decide any changes in the schedule
  • Dosage adjustments may be required problems with heart, kidneys, liver, lungs, nerve pain, or low blood counts 
General Carfilzomib (Kyprolis) Side Effects
  • Heart or kidney problems: report any leg or ankle swelling to your physician
  • Fatigue
  • Nausea and vomiting
  • Low platelet count, which could increase bleeding
  • Shortness of breath
  • Diarrhea or constipation, be cautious of both
  • Infection of nose and throat, cough (upper respiratory system)
  • Headache
  • Legs and arms swelling
  • Fever due to low white blood cell count
  • Back pain
  • Trouble sleeping
  • Click on the carfilzomib (Kyprolis) package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaFatigue Fatigue BleedingBleedingConstipationConstipationPainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Revlimid® (Lenalidomide)

  • Revlimid ​Is a capsule
  • Is not to be used during pregnancy; it may cause human embryo toxicity and birth defects. Females must avoid pregnancy while taking this and for 4 weeks after finishing therapy 
  • Is only available through the R.E.M.S. program, which is Risk Evaluation and Mitigation Strategy http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm 
  • Women should not breast feed while on this drug
  • Can cause severe low white blood cells and platelet cell counts. Patients who have “del 5q myelodysplastic syndromes” should have complete blood counts (CBC) monitored every week for the first eight weeks of treatment
  • Patients may require dose decreases and periodic stopping of doses for low blood cell counts, poor kidney function, or other reasons
  • Some patients may require growth factors to help stimulate blood cell production
  • Patients are at increased risk of blood clots in limbs (DVT- deep vein thrombosis) or lungs (PE- pulmonary embolism), as well as risk for heart attack and stroke.  A "blood thinner" such as aspirin or warfarin may be prescribed to decrease risk of clots
  • Is swallowed whole with or without food and with a large glass of water; take at the same time every day
  • If you miss a dose and it’s less than 12 hours late, take the dose.  If it’s more than 12 hours late skip the dose.  Do not take two doses at the same time
  • This capsule contains lactose.  Patients should advise their physician if they are lactose intolerant
  • Do not open capsules.  If powder from capsule touches skin, wash immediately with soap and water
  • Should be stored at controlled room temperature
  • May interact with digoxin, estrogen containing therapies, and erythropoietin
  • Has been linked to the development of other cancers in a small number of people
  • Do not donate blood during therapy and for one one month after completion of therapy
General Revlimid (Lenalidomide) side effects
  • Low while blood cells
  • Low platelet cells
  • Blood clots
  • Bleeding
  • Diarrhea
  • Constipation
  • Itching
  • Cough or shortness of breath
  • Skin rash
  • Pain
  • Nausea
  • Fatigue, dizziness
  • Muscle cramps
  • Low red blood cells
  • Swelling of arms and legs
  • Liver toxicity
  • Allergic reactions
  • Tumor Lysis Syndrome (TLS)
  • Click on the Revlimid (lenalidomide) package insert below for reported side effects and possible drug interactions

Side Effect Videos
DiarrheaDiarrheaFatigue Fatigue BleedingBleedingConstipationConstipationPainPainAnemiaAnemiaNeutropenic FeverNeutropenic FeverBlood ClotsBlood Clots

See DailyMed package insert.

Dexamethasone (Decadron®)

  • Dexamethasone is supplied as an oral tablet or oral liquid
  • Dexamethasone may increase the risk of infection. Depending upon how much dexamethasone is taken, antibiotics may be prescribed to help prevent infection
  • Should be taken with food and with a large glass of water to avoid stomach irritation or ulcers
  • Should be taken before 6 p.m. when possible, to avoid trouble falling asleep
  • May decrease the response to vaccines; vaccines may need to be repeated at a later date to obtain maximal response
  • If taken daily for several days or weeks, the dose of dexamethasone may need to be gradually decreased (tapered) to avoid withdrawal symptoms
  • If you miss a dose, take the next dose as soon as possible
  • Should be stored at room temperature
General Dexamethasone (Decadron) Side Effects
  • May cause high blood sugar, weight gain, irritability, high blood pressure, difficulty sleeping, stomach ulcers, bone loss, muscle weakness
  • Click on the dexamethasone (Decadron) package insert below for reported side effects and potential drug Interactions
See DailyMed package insert.

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References

1. Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012;120:1801-1809.

2. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142-152.

Created: October 8, 2015 Updated: September 10, 2018

What is Multiple Myeloma (MM)?

Multiple Myeloma is a disease of the white blood cells, called plasma cells, found in the blood or bone marrow. Plasma cells are a type of white blood cell known as a B-lymphocyte.

Sometimes plasma cells form collections on bone and weaken or destroy it. These are known as "lytic lesions". Multiple Myeloma is a rare condition with an unknown cause. The stage can vary at diagnosis and throughout treatment. Staging is based on the international staging system (ISS). The type and effectiveness of the treatment may depend upon the stage.

NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose which therapy is appropriate for you.

What is a teratogen?

A drug that is known to cause severe birth defects or fetal death. These drugs should NOT be used during pregnancy and patients should avoid becoming pregnant while taking these drugs.

Women, if taking a teratogenic medication, should abstain from heterosexual intercourse or use two forms of reliable contraception at least 4 weeks prior to, during, and for 4 weeks after treatment.

Males (even after vasectomy), if taking a teratogenic medication, must use a latex or synthetic condom during any sexual contact with women of childbearing potential and must not donate sperm for up to 28 days following discontinuation of therapy.

What is the Revlimid® REMS program?

REMS stands for Risk Evaluation and Mitigation Strategy. This program requires that all patients must sign a Patient-Physician agreement form acknowledging pregnancy risks before starting treatment.

If you are woman who can get pregnant, you must have 2 negative pregnancy tests before starting lenalidomide and will have pregnancy tests performed periodically throughout treatment. Lenalidomide (Revlimid®) is only dispensed from certain pharmacies and the pharmacy will contact you before every prescription is dispensed.

A confidential survey must also be taken every month before lenalidomide can be dispensed.

Common CRd doses

  • Carfilzomib 20 mg/m2 (max of 44 mg) intravenous (I.V.) injection over 10 minutes on Days 1 & 2 of Cycle 1
    • then, Carfilzomib 27 mg/m2 (max of 59.4 mg) I.V. over 10 min. on Days 8, 9, 15, and 16 of Cycle 1
    • then, Carfilzomib 27 mg/m2 (max of 59.4 mg) I.V. over 10 min. on Days 1, 2, 8, 9, 15, and 16 of Cycles 2 - 12
    • then, Carfilzomib 27 mg/m2 (max of 59.4 mg) I.V. over 10 min. on Days 1, 2, 15, 16 only of Cycles 13 - 18 (no Day 8 or 9)
  • Lenalidomide 25 mg by mouth once daily for 21 days continuously on Days 1 - 21
  • Dexamethasone 40 mg (ten 4 mg tablets) by mouth once daily on Days 1, 8, 15, and 22 of each cycle

Cycle length is 28 days.

Note: Individual doses may vary based upon your Doctor's recommendation, or drug availability

What is a CBC?

A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.

Common uses:
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.

2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.

3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.

What is a CMP?

A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.

Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride

Kidney Function:
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)

Liver Function:
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein

Blood sugar:
13) Serum glucose

Calcium:
14) Serum calcium

What does Cure mean?

The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.

Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.