Treatment Name: IBR (Ibrutinib + Bendamustine + Rituximab)
IBR (Ibrutinib + Bendamustine + Rituximab) is a Chemotherapy Regimen for Chronic Lymphocytic Leukemia (CLL)
How does IBR work?
- Ibrutinib is an oral chemotherapy medication designed to cause cancerous B-lymphocytes to leave both the bone marrow and lymph nodes, and enter the bloodstream where they die more quickly
- Bendamustine is an injectable (I.V.) chemotherapy drug designed to slow the growth of new cancer cells and kill existing cancerous B-lymphocytes
- Rituximab is designed to bind to a specific protein on the surface of cancerous cells, specifically B-lymphocytes, and target these cells for destruction by your immune system. This is commonly known as immunotherapy
I – Ibrutinib (Imbruvica®)
B – Bendamustine (Bendeka®)
R – Rituximab
Goals of therapy:
IBR is given to decrease the size of lymph nodes, decrease the size of an enlarged liver or spleen, or to increase the number of good cells made in the bone marrow. Patients may benefit from increased appetite, disappearance of swollen lymph nodes, and improvement in normal blood cell counts. IBR is commonly taken to control symptoms from CLL or prevent CLL from progressing (getting worse) but is not commonly given with the goal of cure.
Bendamustine and rituximab (the B and R in IBR) are 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. Ibrutinib is usually taken at home.
- Bendamustine intravenous (I.V.) infusion is given over 10 minutes on Days 2 and 3 of Cycle 1; then on Days 1 and 2 of Cycles 2 through 6
- Rituximab I.V. infusion is given on Day 1 of every cycle. The time of infusion varies depending upon tolerability
- Ibrutinib 420 mg tablet by mouth once daily, every day of the week
Estimated total infusion time for this treatment:
- Up to 8 hours for Cycle 1, Day 1; as short as 1 hour for Cycle 1, Days 2 and 3
- If rituximab is well tolerated, up to 2 hours for Day 1 and as short as 1 hour for Day 2 of Cycles 2 through 6
- Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability. Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time
IBR is repeated every 28 days. This is known as one Cycle. Each cycle may be repeated up to six times, depending upon the stage of the disease. Duration of therapy may last up to six months, depending upon response, tolerability, and number of cycles prescribed. After six cycles of IBR are given, ibrutinib may be continued alone until it no longer works or until unacceptable side effects occur.
Click here for the common IBR starting doses.
Note: Individual doses may vary based upon your Doctor's recommendation, or drug availability. For patients who prefer to take capsules, ibrutinib is available in capsule formulation. The most commonly recommended dosage is ibrutinib 420 mg (three 140 mg capsules) by mouth once daily, every day of the week. Typically, all 3 capsules are taken all at once, and around the same time each day.
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 IBR are shown here:
- Low white blood cells [neutropenia] (59%)
- Nausea (37%)
- Diarrhea (35%)
- Low platelets [thrombocytopenia, increased bleeding risk] (31%)
- Bleeding [non-life threatening] (28%)
- Fever (24%)
- Low red blood cells [anemia] (22%)
- Fatigue (21%)
- Cough (19%)
- Constipation (19%)
- Skin rash (18%)
- Infusion reaction (16%)
- Sinus infection (16%)
- Headache (15%)
- Vomiting (14%)
- Bronchitis (12%)
- Decreased appetite (13%)
- Pneumonia (13%)
- Swelling in arms and feet (12%)
- Stomach pain (12%)
- Neutropenic fever (12%)
- Muscle spasms (12%)
- Joint aches (11%)
- Chills (11%)
- Back pain (11%)
- Increase in uric acid in the blood (10%)
- Itching (10%)
- Atrial fibrillation (7%)
- Shortness of breath (6%)
- Blurry vision (5%)
- Bleeding [life-threatening] (up to 4%)
- Cataracts (3%)
On average, 14% of patients discontinue treatment due to unacceptable side effects
If atrial fibrillation develops after beginning therapy with ibrutinib, your doctor may advise that you continue ibrutinib therapy, or stop for a short time, or change ibrutinib to an alternative medication if you prefer. Ibrutinib-related atrial fibrillation can be managed via a number of different ways. Four of 289 (1%) of patients in the clinical trial discontinued ibrutinib due to atrial fibrillation.
How often is monitoring needed?
Labs (blood tests) may be checked before treatment cycle and in between cycles at the discretion of your doctor. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), Lactate Dehydrogenase (LDH), phosphorous, uric acid, plus any others your doctor may order. Hepatitis B screening may also be done before starting treatment. Because ibrutinib can cause bruising or bleeding in up to 50% of patients, a baseline measurement of your body's blood clotting may be needed. These tests commonly include the PT (Prothrombin Time) and the aPTT (activated Partial Thromboplastin Time).
Tumor lysis syndrome may occur. Depending on baseline uric acid level and LDH level, the drug, allopurinol, may need to be taken to help your kidneys eliminate uric acid.
How often is imaging needed?
Imaging may be checked before treatment begins, or as recommended by your doctor. Imaging may include: X-rays, magnetic resonance imaging (MRI), or computerized tomography (CT) scans. Re-imaging scans may be recommended every twelve weeks to assess response to chemotherapy.
How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue IBR as planned, reduce the dose of future treatments, delay the next dose until the side effect goes away, or switch to an alternative therapy.
- 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 premedications are given to help prevent this. Reactions generally go away when the rituximab infusion is stopped. When symptoms go away, it may be restarted at a slower rate. If a reaction occurs, most patients are still able to receive the entire dose of rituximab, although it may take longer. In some cases, after the first dose, it can be give over as short as 90 minutes
- Patients should contact their doctor immediately if they develop lightheadedness or feel their heart racing
- Food increases absorption of ibrutinib by 2-fold so it is best to take on an empty stomach to avoid an increase in side effects
- Consider taking ibrutinib at bedtime since it may cause nausea. All three capsules should be taken at the same time
- As ibrutinib may increase the risk of bleeding, it is important to tell the hematologist when you are having surgery or dental work and what type. They will then consider the risks versus benefits of temporarily holding ibrutinib therapy for up to 3 to 7 days pre and post-surgery or dental procedure. The length of time to hold ibrutinib will depend upon the type of surgery and the risk of bleeding
- Talk to your healthcare provider before eating grapefruit or drinking grapefruit juice, Squirt, Fresca, Sundrop, or things that say “citrus blend” as these may increase the risk of side effects
- High blood pressure may occur in patients taking ibrutinib. If the blood pressure increases, it often does so after about 4 months of taking ibrutinib. If you are already taking medications for blood pressure, the doses may need to be adjusted when adding ibrutinib, or changed to a different blood pressure medication if they interact with ibrutinib
- Ibrutinib may cause fingernail changes such as splitting or cracking. Toenails may also become more brittle and it may take a few months longer to notice these changes. In addition, hair may change in texture and may be noticeable between 6 - 12 months after starting ibrutiinb. Some people have tried taking biotin (vitamin B7, an over-the-counter supplement) to help restore normal nail growth. Talk to your doctor before trying biotin for ibrutinib-related nail changes
- Bendamustine may cause mild irritation to the vein during infusion
- Let your doctor know if you are allergic to polyethylene glycol 400, propylene glycol, or monothioglycerol before receiving bendamustine as this is a related ingredient in the drug product
- A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
- Clinical trials may exist for CLL. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov 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 IBR (Ibrutinib + Bendamustine + Rituximab), 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 IBR (Ibrutinib + Bendamustine + Rituximab). Depending upon your income, they may be able to help cover the cost of:
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 IBR (Ibrutinib + Bendamustine + Rituximab) 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.
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 IBR (Ibrutinib + Bendamustine + Rituximab)
What is Chronic Lymphocytic Leukemia (CLL)?
Chronic Lymphocytic Leukemia (CLL) is the most common type of leukemia diagnosed in adults. It is a cancer of the B-lymphocyte. In rare cases, CLL may be hereditary, but most causes are unknown. The stage of CLL can vary at diagnosis and throughout treatment. Stages of CLL include Rai stage 0, I, II, III, or IV. Many therapies are not curative, however, newer therapies are able to suppress the cancer for many months or even years.
As depicted in the picture, CLL may affect lymph nodes, the spleen, bone marrow, and the blood.
Medications for CLL may include intravenous infusions, oral tablets or capsules, or a combination of IV and oral medications. Patients may be diagnosed with CLL without having any symptoms. Others may go to their doctor with symptoms of fatigue, 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 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.
Common IBR Starting Doses
- Bendamustine 70 mg/m2 intravenous (I.V.) infusion is given over 10 minutes on Days 2 and 3
- Rituximab 375 mg/m2 I.V. infusion is given on Day 1. The time of infusion varies depending upon tolerability
- Ibrutinib 420 mg tablet (or three 140 mg capsules) by mouth once daily, every day of the week
- Bendamustine 70 mg/m2 I.V. infusion is given over 10 minutes on Days 1 and 2
- Rituximab 500 mg/m2 I.V. infusion is given on Day 1. The time of infusion varies depending upon tolerability
- Ibrutinib 420 mg tablet (or three 140 mg capsules) by mouth once daily, every day of the week
Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol 2016;17:200-211.
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.
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 status, 2) 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
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein
13) Serum glucose
14) Serum calcium
What is Tumor Lysis Syndrome (TLS)?Tumor lysis syndrome, or TLS, occurs when many cancer cells die quickly and release their contents into the bloodstream. Many times the body has the ability to flush these substances out through the kidneys or metabolize them via the liver. However, sometimes the body needs medicines to help eliminate these substances and to prevent organ damage.
Ibrutinib-Related Atrial Fibrillation (Afib)
Click here for a proposed algorithm for managing ibrutinib-related afib