Betibeglogene autotemcel
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From MedlinePlus, U.S. National Library of Medicine
Dosing in kidney impairment
Renal Impairment ZYNTEGLO has not been studied in patients with renal impairment. Patients should be assessed for renal impairment, defined as creatinine clearance ≤ 70 mL/min/1.73 m 2 , to ensure HSC transplantation is appropriate.
Dosing in liver impairment
Hepatic Impairment ZYNTEGLO has not been studied in patients with hepatic impairment. Patients should be assessed for hepatic impairment to ensure HSC transplantation is appropriate.
Preparation and administration
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Dose ZYNTEGLO is provided as a single dose for infusion containing a suspension of CD34+ cells in one or more infusion bags. The minimum recommended dose of ZYNTEGLO is 5.0 × 10 6 CD34+ cells/kg. See the Lot Information Sheet provided with the product shipment for additional information pertaining to dose.
Preparation Before ZYNTEGLO Infusion Before mobilization, apheresis, and myeloablative conditioning are initiated, confirm that hematopoietic stem cell (HSC) transplantation is appropriate for the patient. It is recommended that patients be maintained at a hemoglobin (Hb) ≥ 11 g/dL for at least 30 days prior to mobilization and 30 days prior to myeloablative conditioning.
Granulocyte-colony stimulating factor (G-CSF) and plerixafor were used for mobilization and busulfan was used for myeloablative conditioning. Refer to the prescribing information for the mobilization agent(s) and the myeloablative conditioning agent(s) prior to treatment. Perform screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotrophic virus 1 & 2 (HTLV-1/HTLV-2), and human immunodeficiency virus 1 & 2 (HIV-1/HIV-2) in accordance with clinical guidelines before collection of cells for manufacturing.
Mobilization and Apheresis Patients are required to undergo HSC mobilization followed by apheresis to obtain CD34+ cells for product manufacturing. The target number of CD34+ cells to be collected is ≥ 12 × 10 6 CD34+ cells/kg. If the minimum dose of 5.0 × 10 6 CD34+ cells/kg is not met, the patient may undergo additional cycles of mobilization and apheresis, separated by at least 14 days, in order to obtain more cells for additional manufacture.
Up to two drug product lots may be administered to meet the target dose. A back-up collection of CD34+ cells of ≥ 1.5 × 10 6 CD34+ cells/kg (if collected by apheresis) or > 1.0 × 10 8 TNC/kg (Total Nucleated Cells, if collected by bone marrow harvest) is required. These cells must be collected from the patient and be cryopreserved prior to myeloablative conditioning.
The back-up collection may be needed for rescue treatment if there is: 1) compromise of hematopoietic stem cells or ZYNTEGLO before infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with ZYNTEGLO. Myeloablative Conditioning Full myeloablative conditioning must be administered before infusion of ZYNTEGLO.
Consult prescribing information for the myeloablative conditioning agent(s) prior to treatment. Stop iron chelation at least 7 days prior to myeloablative conditioning. Prophylaxis for hepatic veno-occlusive disease (VOD) is recommended [see Clinical Studies ] . Prophylaxis for seizures should be considered, as appropriate.
Do not begin myeloablative conditioning until the complete set of infusion bag(s) constituting the dose of ZYNTEGLO has been received and stored at the treatment center and the availability of the back-up collection is confirmed. After completion of the myeloablative conditioning, allow a minimum of 48 hours of washout before ZYNTEGLO infusion.
Receipt and Storage of ZYNTEGLO ZYNTEGLO is shipped to the treatment center in the vapor phase of liquid nitrogen shipper. Confirm patient identifiers on the product label(s) and Lot Information Sheet within the shipper. If there are any concerns about the product or packaging upon receipt, contact Genetix Biotherapeutics at 1-833-999-6378.
Keep the infusion bag(s) in the metal cassette(s) and transfer ZYNTEGLO from the vapor phase of liquid nitrogen shipper to the treatment center vapor phase of liquid nitrogen storage at ≤ -140°C (≤ -220°F). Store in the vapor phase of liquid nitrogen at ≤ -140°C (≤ -220°F) until ready for thaw and administration. Preparation of ZYNTEGLO for Infusion Coordinate the timing of ZYNTEGLO thaw and infusion.
Confirm the infusion time in advance and adjust the start time of ZYNTEGLO thaw such that it will be available for infusion when the patient and healthcare providers are ready. 1. Remove each metal cassette from liquid nitrogen storage and remove each infusion bag from the metal cassette. 2. Confirm that ZYNTEGLO is printed on the infusion bag(s). 3.
Confirm that patient identity matches the unique patient identifiers located on the ZYNTEGLO infusion bag(s). Do not infuse ZYNTEGLO if the information on the patient-specific label on the infusion bag does not match the intended patient, and contact Genetix Biotherapeutics at 1-833-999-6378. 4. Ensure the correct number of infusion bags are present.
Use the accompanying Lot Information Sheet to confirm that each infusion bag is within the expiration date. 5. Inspect each infusion bag for any breaches of integrity before thawing and infusion. If an infusion bag is compromised, follow the local guidelines and contact Genetix Biotherapeutics immediately at 1-833-999-6378. 6.
If more than one infusion bag is provided, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag. 7. Thaw ZYNTEGLO at 37°C (98.6°F) in a water bath or dry bath. Thawing of each infusion bag takes approximately 2 to 4 minutes. Do not leave ZYNTEGLO unattended. Do not submerge the infusion ports in a water bath. 8.
After thaw, mix the contents gently by massaging the infusion bag to disperse clumps of cellular material until all of the contents are uniform. If visible cell clumps remain, continue to gently mix the contents of the bag. Most small clumps of cellular material should disperse with gentle manual mixing. Do not filter, wash, spin down and/or resuspend ZYNTEGLO in new media prior to infusion. 9.
Do not sample, alter, irradiate or refreeze ZYNTEGLO.
Administration ZYNTEGLO is for autologous use only. The patient's identity must match the patient identifiers on the ZYNTEGLO cassette(s) and infusion bag(s). Do not infuse ZYNTEGLO if the information on the patient-specific label does not match the intended patient. Product must be administered within 4 hours after thawing.
Do not use an in-line blood filter or an infusion pump. 1. Before infusion, confirm that the patient's identity matches the unique patient identifiers on the ZYNTEGLO infusion bag(s). Use the Lot Information Sheet to confirm the total number of infusion bags to be administered. 2. Expose the sterile port on the infusion bag by tearing off the protective wrap covering the port. 3.
Access the infusion bag and infuse ZYNTEGLO as soon as possible after thawing and complete the infusion within 4 hours. 4. Administer each infusion bag of ZYNTEGLO via intravenous infusion over a period of less than 30 minutes. If more than one infusion bag is provided, administer each infusion bag completely before proceeding to thaw and infuse the next infusion bag. 5.
Flush all ZYNTEGLO remaining in the infusion bag(s) and any associated tubing with at least 50 mL of 0.9% sodium chloride solution to ensure that as many cells as possible are infused into the patient. After ZYNTEGLO Administration Standard procedures for patient management after HSC transplantation should be followed after ZYNTEGLO infusion.
Irradiate any blood products required within the first 3 months after ZYNTEGLO infusion. Granulocyte-colony stimulating factor (G-CSF) is not recommended for 21 days after ZYNTEGLO infusion. Restarting iron chelation after ZYNTEGLO infusion may be necessary and should be based on clinical practice [see Drug Interactions and Clinical Studies ] .
Phlebotomy can be used in lieu of iron chelation, when appropriate. Patients should not donate blood, organs, tissues, or cells at any time in the future. ZYNTEGLO contains human blood cells that are genetically modified with replication-incompetent, self-inactivating lentiviral vector. Follow universal precautions and biosafety guidelines (Biosafety Level 2) for handling and disposal of ZYNTEGLO to avoid potential transmission of infectious diseases.
Drug interactions
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No formal drug interaction studies have been performed. ZYNTEGLO is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Anti-retrovirals and Hydroxyurea : Do not take anti-retroviral medications or hydroxyurea for one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed ( 7.2 ) Iron Chelation: Discontinue iron chelators 7 days prior to initiation of myeloablative conditioning. Avoid use of myelosuppressive iron chelators for 6 months after ZYNTEGLO infusion. ( 7.3 )
7.1 Live Vaccines Follow institutional guidelines for vaccine administration. The safety of immunization with live viral vaccines during or following ZYNTEGLO treatment has not been studied.
7.2 Anti-retrovirals and Hydroxyurea Patients should not take anti-retroviral medications or hydroxyurea for at least one month prior to mobilization or the expected duration for elimination of the medications, and until all cycles of apheresis are completed [see Warnings and Precautions (5.5) ] . Anti-retroviral medications may interfere with manufacturing of the apheresed cells.
7.3 Iron Chelation Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates. Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators .
Phlebotomy can be used in lieu of iron chelation, when appropriate [see Clinical Studies (14) ] .
7.4 Erythropoiesis-Stimulating Agents There is no clinical experience with the use of erythropoiesis-stimulating agents in patients treated with ZYNTEGLO.
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary There are no available data with ZYNTEGLO administration in pregnant women. Consider the risks associated with myeloablative conditioning agents on pregnancy and fertility. No reproductive and developmental toxicity studies in animals have been conducted with ZYNTEGLO to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known whether ZYNTEGLO has the potential to be transferred to the fetus. Therefore, ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician.
No nonclinical germline transmission studies have been conducted with ZYNTEGLO. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
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