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Treatment Name: Rituximab + Lenalidomide (Revlimid®)

Rituximab + Lenalidomide (Revlimid®) is a Chemotherapy Regimen for Lymphoma, Mantle Cell

How does rituximab + lenalidomide work?
Rituximab is an antibody that is designed to target and bind to a protein on the surface of cancerous b-cells. When rituximab binds to this protein, it helps your  immune system destroy the cancer cell. This is commonly called immunotherapy.

Lenalidomide is designed to kill cancerous lymphoma cells and to improve the ability of the immune system to target cancerous lymphoma cells.

Goals of therapy:
Rituximab + lenalidomide is given to shrink lymph nodes and decrease symptoms from mantle cell lymphoma such as an enlarged spleen. It is not commonly given with the goal of cure, but to put the lymphoma in remission and keep it in remission.

Alternative names:
R-Squared, R2


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Induction phase

  • Rituximab intravenous (I.V.) infusion once weekly for 4 weeks (four doses), then once every 8 weeks (for five doses). The time of infusion varies depending upon tolerability
  • Usual lenalidomide starting dose: 20 mg oral capsule by mouth daily for 21 consecutive days, then seven days off. Dose may be increased to 25 mg if Cycle 1 is well tolerated
  • Note: The first 4 doses are given over one month, while the following 5 doses are given over ten months

Maintenance phase

  • Rituximab I.V. infusion is given every 8 weeks = 56 days. The time of infusion varies depending upon tolerability
  • Usual lenalidomide starting dose: 15 mg oral capsule by mouth daily for 21 consecutive days, then seven days off
  • Each Cycle of lenalidomide is repeated every 28 days, while each dose of rituximab is repeated every 56 days

Estimated total infusion time for this treatment:

  • Up to eight hours for Cycle 1, Day 1; as short as 90 minutes for the first day of next cycles if well tolerated
  • Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability. Pre-medications and I.V. fluids, such as hydration, may add more time

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).

Rituximab is usually given in an outpatient infusion center, allowing the person to go home afterwards. On occasion, it may be given in the hospital if someone is too sick for outpatient care. Lenalidomide is usually taken at home.

The induction phase of Rituximab + lenalidomide consists of 11 months of treatment, then patients continue on to the maintenance phase where therapy is continued until the regimen no longer is working or until unacceptable side effects occur. Duration of therapy depends upon response, tolerability, and number of cycles prescribed.

Click here for the common rituximab + lenalidomide starting doses. Note: starting doses of lenalidomide may need to be reduced for decreased kidney function.

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 of rituximab + lenalidomide are shown here: 

  • Low white blood cells [neutropenia] (74%)
  • Fatigue (74%)
  • Rash (66%)
  • Anemia [low red blood cells] (60%)
  • Fever (58%)
  • Cough (55%)
  • Diarrhea (55%)
  • High blood sugar (50%)
  • Constipation (45%)
  • Fluid retention (42%)
  • Increased bleeding risk [low platelets] (39%)
  • Sinus infection (39%)
  • Lymph node inflammation [tumor flair] (34%)
  • Infusion reaction (34%)
  • Nausea (32%)
  • Decreased appetite (29%)
  • Shortness of breath (29%)
  • Urinary tract infection [UTI] (18%)
  • Decreased thyroid function (16%)
  • Inflammation of the sinuses (11%)
  • Skin infection (8%)
  • Pneumonia (8%)
  • Neutropenic fever (5%)

Approximately 10% of patients discontinue either rituximab or lenalidomide treatment due to unacceptable side effects. In most cases, if treatment with one agent is discontinued the other agent may still be continued.

Side effect videos Side Effect Videos
Fatigue Fatigue AnemiaAnemiaDiarrheaDiarrheaConstipationConstipationNausea and VomitingNausea and VomitingNeutropenic FeverNeutropenic FeverPainPain


How often is monitoring needed?
Labs (blood tests) may be checked before treatment then periodically during treatment. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), plus any others your doctor may order. Hepatitis B screening and Human Immunodeficiency Virus (HIV) screening may also be done before starting treatment.

How often is imaging needed?
Imaging may be checked before treatment then approximately every three months for two years, then every six months thereafter. Imaging may include: computerized tomography (CT) scans or positron emission tomography (PET) scans.

How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue rituximab + lenalidomide as planned, reduce the dose of future treatments, delay the next dose until the side effect goes away, or switch to an alternative therapy.

Questions to Ask Your...

A better understanding of your treatments will allow you to ask more questions of your healthcare team. We then hope that with the answers, you will get better results and have greater satisfaction with your care. Because we know it's not always easy to know what questions to ask, we've tried to make it easy for you!

Choose any healthcare provider below to see common questions that you may want to ask of this person. Then, either print each list to bring to your clinic visits, or copy the questions and send them as a message to your healthcare team through your electronic medical record.

ChemoExperts Tips

  • 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 enoxaparin may be prescribed to decrease risk of clots
  • Premedications such as diphenhydramine (Benadryl®), acetaminophen (Tylenol®), and hydrocortisone (Solu-Cortef®) may be given before rituximab to help avoid infusion related reactions
  • The first dose of rituximab is often the hardest. It may lead to fever, shaking, and chills even if medications are given beforehand to help prevent these side effects. Side effects generally go away when the rituximab is stopped. It may then be restarted at a slower rate. Most patients are able to receive the entire dose, although it may take longer. In most cases, after the first dose is well tolerated, rituximab can be given over 90 minutes
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for Mantle Cell Lymphoma. Ask your doctor if any studies are currently enrolling in your area. If not, go to to search for 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 Rituximab + Lenalidomide (Revlimid®), 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 Rituximab + Lenalidomide (Revlimid®). Depending upon your income, they may be able to help cover the cost of:

  • Rituximab
  • Lenalidomide

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 Rituximab + Lenalidomide (Revlimid®) 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 Rituximab + Lenalidomide (Revlimid®)

Individual Drug Label Information

Rituximab (Rituxan®, Truxima®, Ruxience®)

  • Rituximab is an intravenous infusion
  • Acetaminophen (Tylenol®) and antihistamines (e.g. diphenhydramine = Benadryl®) should be given prior to each dose
  • Patients should be screened for hepatitis B as rituximab can cause a re-activation of this infection
  • May cause vaccines to work less well for 6 - 12 months after the last dose of rituximab. It is advised that vaccines be given two to four weeks prior to rituximab if possible
General Rituximab Side Effects
  • May cause an infusion reaction, which could include skin reaction, shaking, chills, fever, or shortness of breath. These reactions may be severe, but are very rarely life-threatening Infusion reactions does not usually happen after the first dose, but are possible
  • May increase the risk of infection. Your doctor may prescribe antibiotics to prevent certain infections associated with rituximab use
  • Click on the rituximab package insert below for reported side effects and potential drug Interactions

Side Effect Videos
Fatigue Fatigue

See DailyMed package insert.

Lenalidomide (Revlimid®)

  • Lenalidomide 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 
  • 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 Lenalidomide (Revlimid) 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 lenalidomide (Revlimid) 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.

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Ruan J, Martin P,  Shah B, et al. Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma. N Engl J Med. 2015 Nov 5;373(19):1835-44.

Created: May 3, 2017 Updated: October 24, 2018

What is Lymphoma, Mantle Cell?

Mantle Cell lymphoma (MCL) is one of about 30 sub-types of Non-Hodgkin Lymphoma. MCL represents up to 8% of all diagnosed lymphomas. It is a cancer of the B-lymphocyte. Most patients who have MCL are 60 years old or greater and more commonly male than female. Many patients are diagnosed with swollen lymph nodes in the neck, armpit, or groin, or an enlarged spleen, which may cause fullness under the left rib cage or abdominal pain.

The cause(s) of MCL are unknown. The stage of MCL can vary at diagnosis and throughout treatment. Stages of MCL include stage I, II, III, or IV. Although therapies are usually given with curative intent, many times the lymphoma returns within 1 – 2 years. Stem cell transplant and combined, multi-drug therapies are usually more effective than single medications.

Medications for MCL may include intravenous infusions, oral tablets or capsules, or a combination of IV and oral medications. Patients may be diagnosed with MCL without having any symptoms. Others may go to their doctor with symptoms of swollen lymph nodes, a large spleen, or decreased appetite. The effectiveness of the treatment may depend upon the stage at diagnosis.

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 an Antibody?

An antibody is a small protein shaped like a “Y” that can attach to specific things in the blood, such as a cancer cell.
  • Once an antibody binds to something, your immune system may attempt to get rid of it.
  • Antibodies may also work by binding to the cancer cell surface and prevent other things from binding to the cancer cell that help it survive. Without the ability to bind growth factors, cancer cells may be forced to die"

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.

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 female who can get pregnant, you must have 2 negative pregnancy tests before starting Revlimid® and will have pregnancy tests performed periodically throughout treatment. 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 Revlimid® can be dispensed.

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

14) Serum calcium

Common Starting Doses

Induction phase

  • Rituximab 375 mg/m2 intravenous (I.V.) infusion once weekly for four weeks (4 doses), then once every eight weeks (for five doses). The time of infusion varies depending upon tolerability
  • Usual lenalidomide starting dose: 20 mg oral capsule by mouth daily for 21 consecutive days, then seven days off. Dose may be increased to 25 mg if Cycle 1 is well tolerated
  • Cycle is 28 days 

Maintenance phase 

  • Rituximab 375 mg/m2 I.V. infusion every 8 weeks. The time of infusion varies depending upon tolerability
  • Usual lenalidomide starting dose: 15 mg oral capsule by mouth daily for 21 consecutive days, then seven days off
  • Cycle is 28 days

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