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 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
I – Ibrutinib (Imbruvica®)
B – Bendamustine (Bendeka®)
R – Rituximab (Rituxan®)
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 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)