1. What is KRESLADI?
KRESLADI is a stem cell-based gene therapy used to treat pediatric patients with severe leukocyte adhesion deficiency type I (LAD-I) without an available human leukocyte antigen (HLA)-matched sibling donor for stem cell transplant. LAD-I is a genetic, lifelong disease caused by a change in the ITGB2 gene which causes the body to produce blood cells that cannot fight infections.
KRESLADI is made specifically for each patient, using the patient’s own modified blood stem cells, and adds functional copies of the ITGB2 gene to your cells. This may help the body to produce cells that can better fight infections.
KRESLADI was approved under accelerated approval based on an increase in CD18 and CD11a expression after treatment with KRESLADI. Additional data are needed to confirm the clinical benefit of KRESLADI.
2. What is the most important information I should know about KRESLADI?
It’s important to talk to your healthcare provider about the risks and benefits of all medicines involved in your treatment.
Your healthcare provider will give you other medicines, including conditioning medicine as part of your treatment with KRESLADI. You may experience side effects associated with other medicines administered as part of the treatment regimen for KRESLADI. Conditioning medicine may put you at an increased risk for low blood counts, infections, bleeding, or other serious side effects.
After treatment with KRESLADI, you will have fewer white blood cells (cells that help to fight infections) for a while until engraftment (successful attachment and growth of transplanted cells).
Your healthcare provider will monitor you for signs and symptoms of infection and give you treatment as required.
Tell your healthcare provider right away if you experience any of the following, which could be signs of infections:
-
Fever
- Sweats or Chills
- Cough or flu-like symptoms
- Muscle aches
- Warm, red, painful areas on the skin
You also may be at increased risk of veno-occlusive disease (blocked liver flow) due to the conditioning medicine.
Your healthcare provider will monitor your liver with blood tests during the first month after KRESLADI infusion. Tell your healthcare provider right away if you experience any of the following, which could be signs of blocked liver flow:
- Rapid, unexplained weight gain
- Fluid buildup in the abdomen
- Jaundice (yellowing of the skin or whites of the eyes)
- Severe tender enlargement of the liver
In some patients, the modified cells may not engraft (take hold). Your healthcare provider will monitor your blood tests to determine if the modified cells have taken hold. If the modified cells do not take hold, you may need to receive back-up cells that were collected before treatment.
After treatment with KRESLADI, you may have fewer platelets (cells that can help the body stop bleeding and seal wounds) for a while until the modified cells take hold, which may increase the risk for bleeding. Your healthcare provider will monitor your blood tests after treatment.
Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of platelets:
- Severe headache
- Abnormal bruising
- Prolonged bleeding
- Bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood
KRESLADI may increase your risk of getting cancers including certain types of blood cancer. It is important that you have regular check-ups with your healthcare provider, this may require you to have more frequent blood tests (at least once a year for at least 15 years and as advised by your healthcare provider). You may also need to have invasive bone marrow biopsies if the routine blood tests are concerning for the development of blood cancer.
Serious allergic reactions, including anaphylaxis, may occur with KRESLADI infusion. Your healthcare provider will monitor you for signs and symptoms of allergic reaction during and after KRESLADI infusion.
Talk to your physician regarding possible side effects. Your healthcare provider may give you other medicines to treat your side effects.
KRESLADI is manufactured using the patient’s own modified blood stem cells. If you are taking any anti-retroviral medications, such as those used for human immunodeficiency virus (HIV) prevention, it may interfere with the manufacturing of KRESLADI. Treatment with KRESLADI should be delayed until your healthcare provider has ruled out an HIV infection. You should not take anti-retroviral medications for at least one month prior to mobilization and for the expected duration required for elimination and until all cycles of apheresis (blood cell collection) are completed.
KRESLADI will not give you an HIV infection. Treatment with KRESLADI may cause a false-positive HIV test result because of the lentiviral vector used in KRESLADI. If you need to have an HIV test, talk with your healthcare provider about the appropriate test to use.
Do not donate blood, organs, tissues, or cells at any time in the future after receiving KRESLADI.
3. What should I know before treatment with KRESLADI?
It is not recommended to receive vaccinations from the 6 weeks before the start of the KRESLADI treatment process until recovery following treatment. When possible, childhood vaccinations should begin prior to conditioning for KRESLADI.
4. How will I receive KRESLADI?
Phase 1: The KRESLADI treatment process starts with mobilization medicine. This medicine moves blood stem cells from your bone marrow into the blood stream. The blood stem cells are then collected in a machine that separates the different blood cells (this is called apheresis). This entire process may happen more than once. Each time, it can take up to one week.
During this step extra ‘back-up cells’ are also collected and stored at the hospital. These back-up cells are kept untreated just in case there is a problem in the treatment process. If KRESLADI cannot be given after the conditioning medicine, or if the modified blood stem cells do not take hold (engraft) in your body, these back-up cells will be administered to you. If you are given back-up cells, you will not have any treatment benefit from KRESLADI.
Phase 2: After they are collected, your blood stem cells will be sent to the manufacturing site where they are used to make KRESLADI. It typically takes 4-5 Months from the time your cells are collected to make and test KRESLADI before it is sent back to your healthcare provider, but the time may vary.
Phase 3: Shortly before you receive the KRESLADI infusion, your healthcare provider will give you conditioning medicine for a few days in the hospital. This will prepare you for KRESLADI infusion by clearing cells from the bone marrow and making space for the modified cells in KRESLADI. After you are given this medicine, your blood cell levels may fall to very low levels. You will stay in the hospital for this phase and remain in the hospital until after infusion with KRESLADI.
Phase 4: KRESLADI is given into a vein (intravenous infusion). You may receive more than one infusion bag of KRESLADI. Each bag will usually be infused over 10 minutes or less.
After the KRESLADI infusion, you will stay in the hospital so that your healthcare team can closely monitor your recovery. Your healthcare provider will decide when you can go home.
5. What are the possible or reasonably likely side effects of KRESLADI?
The most common side effects of KRESLADI include:
- Mouth and/or throat sores or inflammation
- Upper respiratory tract infection
- Viral infection
- Fever with low white blood cell count
- Skin sores or bruising
- Nausea/vomiting
- Skin rash, redness, or blistering
- Fever (100.4°F/38°C or higher)
- Infection related to the drug delivery equipment
- Skin infection
The most common changes in blood tests that may occur after treatment with KRESLADI include:
- decreased hemoglobin (red blood cells)
- decreased platelet counts (blood cells that help the body to stop bleeding and seal wounds)
- decreased neutrophil counts (white blood cells that help to fight infections)
- decreased leukocyte counts (white blood cells)
- increased aspartate aminotransferase (liver enzyme)
- increased alanine aminotransferase (liver enzyme)
These are not all the possible side effects of KRESLADI. Call your healthcare provider about any side effects that concern you. You are encouraged to report negative side effects of prescription drugs to FDA. Visit http://www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see full Prescribing Information for KRESLADI. Prescribing Information.
