Treatment Name: Inotuzumab Ozogamicin (Besponsa®)

Inotuzumab Ozogamicin (Besponsa®) is a Treatment Regimen for Acute Lymphoid Leukemia (ALL)

How does Inotuzumab Ozogamicin (Besponsa®) work?
Inotuzumab ozogamicin is an antibody that targets leukemia cells. Once it binds to the leukemia cell surface, it then enters the inside of the cancer cell. Once inside the cell, the antibody releases a drug called calicheamicin, which damages the DNA of the leukemia cell and causes the cell to die.

Goals of therapy:
Inotuzumab ozogamicin is given to kill leukemia cells and restore normal bone marrow activity. It is given with the goal of achieving disease remission, and possibly a cure, in patients who have relapsed or who are refractory after at least one prior treatment for ALL. If remission is achieved, some patients may receive a bone marrow transplant with the goal of cure.

Schedule

Inotuzumab ozogamicin intravenous (I.V.) infusion over 60 minutes on Days 1, 8, and 15

Estimated total infusion time for this treatment:

Up to 2 hours for Days 1, 8, and 15 of each cycle (one hour infusion followed by one hour observation period)
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

Inotuzumab ozogamicin 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.

The first cycle of inotuzumab ozogamicin is given over 21 days. All subsequent cycles are given every 28 days. If complete remission is not achieved after three cycles of therapy, inotuzumab ozogamicin is typically stopped.

For patients in remission that are proceeding to bone marrow transplant, inotuzumab ozogamicin may be given for up to three cycles. For patients in remission who are not proceeding to bone marrow transplant, inotuzumab ozogamicin may be given for up to six cycles. Duration of therapy may last up to six months, depending upon response, tolerability, and number of cycles prescribed.

Click here for the common inotuzumab ozogamicin (Besponsa®) starting doses.

Side Effects

In clinical studies, the most commonly reported side effects of inotuzumab ozogamicin are shown here:

Low white blood cells [neutropenia] (48%)
Low platelets [thrombocytopenia] (45%)
Nausea (32%)
Low red blood cells [anemia] (30%)
Headache (28%)
Neutropenic fever (27%)
Fever (27%)
Fatigue (22%)
Diarrhea (18%)
Vomiting (17%)
Constipation (17%)
Nose bleed (15%)
Trouble sleeping (15%)
Stomach pain (14%)
Cough (11%)
Severe liver injury [veno-occlusive disease] (11%)
Chills (10%)
Decreased appetite (9%)
Rash (9%)
Pain in arms or legs (9%)
Dizziness (9%)
Weakness (9%)
Fluid accumulation in arms or legs (9%)
Low blood pressure (8%)
Shortness of breath (5%)

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

Side effect videos
Nausea and VomitingAnemiaPainNeutropenic FeverFatigue DiarrheaConstipationBleeding

Monitoring

How often is monitoring needed?
Labs (blood tests) may be checked before each treatment or more often if needed. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), uric acid, phosphorous, lactate dehydrogenase (LDH), plus any others your doctor may order.

How often is imaging needed?
Imaging may be checked if there are concerns for infection, a blood clot, or bleeding. Imaging may include: X-rays, computerized tomography (CT) scans, or magnetic resonance imaging (MRI). Electrocardiograms, commonly referred to as an ECG or EKG, are used to evaluate the QTc interval prior to therapy and periodically throughout treatment.

How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue inotuzumab ozogamicin (Besponsa®) 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.

Questions to ask your Doctor Nurse Pharmacist

Questions to ask your Nurse Doctor Pharmacist

Questions to ask your Pharmacist Doctor Nurse

ChemoExperts Tips

Inotuzumab ozogamicin can cause a serious liver condition known as veno-occlusive disease (VOD). VOD is more common in patients who receive a bone marrow transplant after receiving therapy with inotuzumab ozogamicin, but it may also occur in patients who don’t receive a transplant. Other risk factors include prior liver disease, increased age, number of prior chemotherapy treatments, and the number inotuzumab ozogamicin treatments given. Contact your doctor immediately if you notice yellowing of the eyes or skin and severe stomach pain or swelling. In some cases, VOD can be treated with a drug called defibrotide (Defitelio®)
Due to the risk of delayed infusion reactions, you may need to be observed in the infusion center for one hour after each inotuzumab ozogamicin infusion is complete
If your blood has a high number of leukemia cells (> 10,000 cells/mm), you may need to receive medications to lower the amount of leukemia cells before inotuzumab ozogamicin can be started. These medications may include hydroxyurea (Hydrea®), vincristine (Oncovin®), or a corticosteroid such as dexamethasone (Decadron®)
Premedications such as diphenhydramine (Benadryl®), acetaminophen (Tylenol®), and hydrocortisone (Solu-Cortef®) may be given before rituximab to help avoid infusion related reactions. You may need to be watched for a reaction for at least one hour after the infusion is complete
A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
Clinical trials may exist for ALL. 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 Inotuzumab Ozogamicin (Besponsa®), 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 Inotuzumab Ozogamicin (Besponsa®). Depending upon your income, they may be able to help cover the cost of:

Inotuzumab Ozogamicin

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 Inotuzumab Ozogamicin (Besponsa®) 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 Inotuzumab Ozogamicin (Besponsa®)

Individual Drug Label Information

Inotuzumab Ozogamicin (Besponsa®)

Is an intravenous infusion
Can cause a serious liver condition known as veno-occlusive disease (VOD)
Contact your doctor immediately if you notice yellowing of the eyes or skin and severe stomach pain or swelling
Can cause heart rhythm problems, which may be fatal. Close monitoring is required to prevent problems. An electrocardiogram (ECG) must be performed to make sure inotuzumab ozogamicin is safe to begin
Dosage adjustments may be required for low blood counts or liver toxicity
May interact with medications known to interfere with heart rhythm. Ask your pharmacist to double check to see if you are taking any of these types of interacting medicines
May cause fetal harm if given while pregnant. Females should use effective contraception during treatment and for at least 8 months (5 months for males) following the completion of treatment. Do not breastfeed during treatment and up to 2 months after the last dose

General side effects from inotuzumab ozogamicin:

Low white blood cells, red blood cells, and platelets
Nausea and vomiting
Headache
Neutropenic fever
Fever and chills
Fatigue and weakness
Diarrhea or constipation
Nose bleed
Trouble sleeping
Stomach pain
Cough
Rash
Click on the Inotuzumab ozogamicin (Besponsa®) package insert below for reported side effects, possible drug interactions, and other inotuzumab ozogamicin prescribing information

Side Effect Videos
Nausea and VomitingDiarrheaFatigue BleedingConstipationPainAnemiaNeutropenic Fever

See DailyMed package insert.

References

1) Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016;375:740-753.

Created: February 14, 2019 Updated: June 24, 2019

What is Acute Lymphoid Leukemia (ALL)?

Acute Lymphoid Leukemia (ALL), also known as acute lymphoblastic leukemia, is a disease of the lymphoid cells found in the bone marrow. Lymphoid cells are responsible for developing into cells of the immune system called B-cells, T-cells, or Natural Killer cells. In ALL, immature lymphoid cells know as "blasts" replicate at a very fast rate. Sometimes blasts crowd out the normal cells in the bone marrow so that red blood cells or platelets are unable to develop.

Common symptoms of ALL include fatigue, infection, and bruising or bleeding. ALL is the most common cancer diagnosed in children, but is rare in adults. Most cases of ALL are considered "de novo" meaning that the cause is unknown; however, some cases can be linked to certain genetic syndromes. There is no staging system for ALL. Chromosomes are often analyzed to determine which mutations in the chromosomes exist. The effectiveness of the treatment may depend upon the specific chromosome mutations that are present.

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 your therapy.

Common inotuzumab ozogamicin (Besponsa®) starting doses

Induction therapy: Inotuzumab ozogamicin 0.8 mg/m² intravenous (I.V.) infusion over 60 minutes on Day 1, then 0.5 mg/m² I.V. infusion over 60 minutes on Days 8 and 15
- If in complete response: Inotuzumab ozogamicin 0.5 mg/m² I.V. infusion over 60 minutes on Days 1, 8, and 15
- If not in complete response: Inotuzumab ozogamicin 0.8 mg/m² I.V. infusion over 60 minutes on Day 1, then 0.5 mg/m² I.V. infusion over 60 minutes on Days 8 and 15

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

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.

Clinical Studies

If you are interested in reading the clinical trials results, please click on references below:

1) Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016;375:740-753.

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 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

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 is QTc interval? Arsenic

The time it takes your heart to make one beat can be measured using an electrocardiogram (ECG, or EKG) and is reported as the QTc interval. Arsenic is generally safe to give when the QTc interval for men is less than 450 milliseconds per beat, and for women, less than 460 milliseconds per beat.

The QTc interval is prolonged if the heart takes too long to make the next beat, and could lead to a dangerous heartbeat known as an arrhythmia.

Certain medications, in addition to arsenic, may prolong the QTc interval. The list includes: ondansetron (Zofran®), Levofloxacin or ciprofloxacin antibiotics. Make sure your pharmacist checks all new medications to make sure they do not prolong the QTc interval.

VOD

Veno-occlusive disease (VOD), otherwise known as sinusoidal obstructive syndrome (SOS), is a serious liver condition where the small blood vessels in the liver are damaged and become blocked by small blood clots. This can cause decreased blood flow through the liver and can severely damage liver cells and lead to liver failure.