Version May 2024
Note: A treatment course consists of multiple phases: 1) Mobilization and apheresis to collect CD34+ cells for manufacturing, 2) Myeloablative conditioning, and 3) Betibeglogene autotemcel infusion, with a minimum of 48 hours washout between busulfan and betibeglogene autotemcel infusion.
For autologous use only; confirm patient identity matches unique patient identifiers on the cassette and infusion bag(s). Betibeglogene autotemcel is provided as a single dose for infusion containing a suspension of CD34+ cells in 1 or more infusion bags; confirm correct number of infusion bags are present (see lot information sheet).
Mobilization: Confirm a negative HIV test prior to beginning mobilization and apheresis of CD34+ cells if antiretrovirals are required for HIV prophylaxis. Patients should not take prophylactic HIV antiretroviral medications or hydroxyurea for at least 1 month prior to mobilization (or for the expected duration for elimination of the medications) and until all cycles of apheresis are completed.
Patients should be maintained at a hemoglobin of ≥11 g/dL for at least 30 days prior to mobilization. Granulocyte colony-stimulating factor (G-CSF) and plerixafor were used for mobilization in clinical trials. The target collection is ≥12 × 106 CD34+ cells/kg; if the minimum CD34+ cell dose is not collected, the patient may undergo additional cycles of mobilization and apheresis (separated by at least 14 days); up to 2 product lots may be administered to meet the target dose. A back-up collection of CD34+ cells (either via apheresis or marrow harvest; refer to product labeling for details) is required for rescue treatment (if needed); collect and cryopreserve prior to myeloablative conditioning.
Myeloablative conditioning preparation: Patients should be maintained at a hemoglobin of ≥11 g/dL for 30 days prior to myeloablation. Discontinue iron chelation therapy at least 7 days prior to myeloablative conditioning (avoid the use of iron chelators for 6 months after betibeglogene autotemcel infusion; if necessary, use non-myelosuppressive iron chelators). Busulfan was used for myeloablative conditioning in clinical trials. Prophylaxis for hepatic sinusoidal syndrome (veno-occlusive disease) is recommended. Anti-seizure prophylaxis should be considered as clinically appropriate. Confirm availability of autologous betibeglogene autotemcel at the infusion center (and availability of back-up collection) prior to initiating myeloablative therapy. Refer to manufacturer labeling for conditioning agents and specific protocols.
Beta thalassemia: Children ≥4 years and Adolescents: IV: Minimum recommended dose: 5 × 106 CD34+ cells/kg; administer after a washout period of at least 48 hours after completion of myeloablative conditioning (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≤70 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; has not been studied in patients with renal impairment.
There are no dosage adjustments provided in the manufacturer's labeling; has not been studied in patients with hepatic impairment.
(For additional information see "Betibeglogene autotemcel: Drug information")
Note: A treatment course consists of mobilization and apheresis to collect CD34+ cells for manufacturing, then busulfan myeloablative conditioning, followed by betibeglogene autotemcel infusion, with a minimum of 48 hours washout between busulfan and betibeglogene autotemcel infusion. For autologous use only; confirm patient identity matches unique patient identifiers on the cassette and infusion bag(s). Betibeglogene autotemcel is provided as a single dose for infusion containing a suspension of CD34+ cells in 1 or more infusion bags; confirm correct number of infusion bags are present (see lot information sheet).
Mobilization: Patients should be maintained at a hemoglobin of ≥11 g/dL for at least 30 days prior to mobilization. Granulocyte colony-stimulating factor (G-CSF) and plerixafor were used for mobilization in clinical trials. If the minimum CD34+ cell dose is not collected (the target collection is ≥12 × 106 CD34+ cells/kg), the patient may undergo additional cycles of mobilization and apheresis (separated by at least 14 days); up to 2 product lots may be administered to meet the target dose. A back-up collection of CD34+ cells (either via apheresis or marrow harvest; refer to product labeling for details) is required for rescue treatment (if needed); collect and cryopreserve prior to myeloablative conditioning. Patients should not take prophylactic HIV antiretroviral medications or hydroxyurea for at least 1 month prior to mobilization (or for the expected duration for elimination of the medications) and until all cycles of apheresis are completed. Confirm a negative HIV test prior to beginning mobilization and apheresis of CD34+ cells if antiretrovirals are required for HIV prophylaxis.
Myeloablative conditioning preparation: Patients should be maintained at a hemoglobin of ≥11 g/dL for 30 days prior to myeloablation. Discontinue iron chelation therapy at least 7 days prior to myeloablative conditioning (avoid the use of iron chelators for 6 months after betibeglogene autotemcel infusion; if necessary, use nonmyelosuppressive iron chelators). Busulfan was used for myeloablative conditioning in clinical trials. Prophylaxis for hepatic sinusoidal syndrome (veno-occlusive disease) is recommended. Antiseizure prophylaxis should be considered as clinically appropriate. Confirm availability of autologous betibeglogene autotemcel at the infusion center (and availability of back-up collection) prior to initiating myeloablative therapy. Refer to product labeling for further information.
Beta thalassemia: Minimum recommended dose: IV: 5 × 106 CD34+ cells/kg (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≤70 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; has not been studied in patients with kidney impairment; however, patients should be evaluated to ensure appropriateness of betibeglogene autotemcel treatment.
There are no dosage adjustments provided in the manufacturer's labeling; has not been studied in patients with hepatic impairment; however, patients should be evaluated to ensure appropriateness of betibeglogene autotemcel treatment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and pediatrics.
>10%:
Dermatologic: Alopecia, dyschromia, pruritus, skin rash
Endocrine & metabolic: Hyperglycemia, hypokalemia, hypophosphatemia
Gastrointestinal: Abdominal pain, constipation, decreased appetite, diarrhea, nausea, stomatitis, vomiting
Hematologic & oncologic: Anemia, febrile neutropenia, leukopenia, lymphocytopenia, neutropenia, thrombocytopenia
Hepatic: Increased serum alanine aminotransferase
Hypersensitivity: Transfusion reaction
Infection: Viral infection
Nervous system: Fatigue, headache, procedural pain
Neuromuscular & skeletal: Musculoskeletal pain
Respiratory: Cough, dyspnea, epistaxis, hypoxia, nasopharyngitis, oropharyngeal pain, rhinitis, upper respiratory tract infection
Miscellaneous: Fever
1% to 10%:
Cardiovascular: Heart failure, hypertension, tachycardia
Endocrine & metabolic: Hyponatremia (grades 3/4)
Gastrointestinal: Dyspepsia, gingivitis
Hepatic: Hepatic sinusoidal obstruction syndrome, hyperbilirubinemia (grades 3/4)
Infection: Sepsis
Respiratory: Pneumonia
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Hypersensitivity: Allergic reactions may occur with betibeglogene autotemcel. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) component.
• Insertional oncogenesis: There is a potential risk of lentiviral vector-mediated insertional oncogenesis following treatment with betibeglogene autotemcel. Patients may develop hematologic malignancies and should be monitored lifelong. If a malignancy occurs, contact the manufacturer (1-833-999-6378) for reporting and to obtain instructions on collection of samples for testing.
• Neutrophil engraftment failure: There is a potential risk of neutrophil engraftment failure after treatment with betibeglogene autotemcel. Neutrophil engraftment failure is defined as failure to achieve 3 consecutive ANCs ≥500/mm3 obtained on different days by day 43 after betibeglogene autotemcel infusion. If neutrophil engraftment failure occurs in a patient treated with betibeglogene autotemcel, provide rescue treatment with the back-up collection of CD34+ cells.
• Platelet engraftment delay: Delayed platelet engraftment has been observed with betibeglogene autotemcel treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia. Grade 3 thrombocytopenia has been observed on or after day 100. Patients should be made aware of the risk of bleeding until platelet recovery has been achieved.
Disease-related concerns:
• Patients with HIV: Betibeglogene autotemcel has not been studied in patients with HIV-1, HIV-2, human T-lymphotropic virus 1 (HTLV-1), or HTLV-2. A negative serology test for HIV is necessary to ensure acceptance of apheresis material to manufacture betibeglogene autotemcel. Apheresis material from patients with a positive HIV test will not be accepted for betibeglogene autotemcel manufacturing.
Concurrent drug therapy issues:
• Immunizations: Follow institutional guidelines for vaccine administration. The safety of immunization with live viral vaccines during or following betibeglogene autotemcel treatment has not been studied.
Dosage form specific issues:
• Dimethyl sulfoxide: Betibeglogene autotemcel contains dimethyl sulfoxide (DMSO), which is associated with serious hypersensitivity reactions, including anaphylaxis.
• Universal precautions: Betibeglogene autotemcel contains human blood cells that are genetically modified with replication-incompetent, self-inactivating lentiviral vector; follow universal precautions and facility biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases.
Other warnings/precautions:
• Appropriate use: After betibeglogene autotemcel administration, the standard procedures for patient management after hematopoietic cell transplantation should be followed. Irradiate any blood products required within the first 3 months after betibeglogene autotemcel infusion. Granulocyte colony-stimulating factor (G-CSF) is not recommended for 21 days after betibeglogene autotemcel infusion. If possible, avoid the use of iron chelators for 6 months after betibeglogene autotemcel infusion; restarting iron chelation after betibeglogene autotemcel infusion may be necessary and should be based on clinical practice; phlebotomy can be used in lieu of iron chelation, when appropriate; if iron chelators are necessary, use nonmyelosuppressive iron chelators. Patients should not donate blood, organs, tissues, or cells at any time in the future.
Zynteglo is composed of up to four infusion bags which contain 2 to 20 × 106 cells/mL suspended in cryopreservation solution. Each infusion bag contains ~20 mL. A single dose of Zynteglo contains a minimum of 5 × 106 CD34+ cells/kg suspended in cryopreservation solution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Zynteglo: (1 ea)
No
Note: For autologous use only; confirm patient identity matches unique patient identifiers on the cassette and infusion bag(s). Betibeglogene autotemcel is provided as a single dose for infusion containing a suspension of CD34+ cells in 1 or more infusion bags; confirm correct number of infusion bags are present (see lot information sheet).
IV: For IV use only. Infuse each bag over <30 minutes. Do not use an inline blood filter or an infusion pump. After infusing each bag, flush all remaining betibeglogene autotemcel remaining in infusion bag and any associated tubing with at least 50 mL NS to ensure that as many cells as possible are infused.
Coordinate the timing of administration with thawing. If more than 1 bag is required, administered each infusion bag completely before proceeding to thaw and infuse the next bag. Infuse as soon as possible after thawing; must be administered within 4 hours after thawing.
IV: For IV use only. Infuse each bag over less than 30 minutes. After infusing each bag, flush all remaining betibeglogene autotemcel remaining in infusion bag and any associated tubing with at least 50 mL NS to ensure that as many cells as possible are infused. Do not use an inline blood filter or an infusion pump.
Coordinate the timing of administration with thawing. If more than one bag is required, administer each infusion bag completely before proceeding to thaw and infuse the next bag. Infuse as soon as possible after thawing; must be administered within 4 hours after thawing.
Keep the infusion bag(s) in the metal cassette(s) and store/transfer in the vapor phase of liquid nitrogen at ≤−140°C (≤−220°F) until ready for thaw and administration. Thaw prior to infusion. Do not re-freeze after thawing. Do not irradiate, as this could lead to inactivation. Product must be administered within 4 hours after thawing.
Treatment of beta thalassemia in patients who require regular red blood cell transfusions (FDA approved in ages ≥4 years and adults).
Betibeglogene autotemcel may be confused with axicabtagene ciloleucel, brexucabtagene autoleucel, ciltacabtagene autoleucel, elivaldogene autotemcel, idecabtagene vicleucel, lisocabtagene maraleucel, sipuleucel-T, tisagenlecleucel.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Antiretroviral Agents: May diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Granulocyte Colony-Stimulating Factors: May interact via an unknown mechanism with Betibeglogene Autotemcel. Management: Granulocyte-colony stimulating factor is not recommended for 21 days after betibeglogene autotemcel infusion. Risk X: Avoid combination
Hydroxyurea: May diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Iron Chelators: May diminish the therapeutic effect of Betibeglogene Autotemcel. Management: Avoid use of iron chelators for at least 7 days prior to conditioning therapy preceding betibeglogene autotemcel treatment, and avoid use of myelosuppressive iron chelators for at least 6 months after betibeglogene autotemcel. Risk X: Avoid combination
Evaluate pregnancy status prior to therapy. Patients who could become pregnant should have a negative serum pregnancy test prior to beginning mobilization, prior to conditioning procedures, and prior to administering betibeglogene autotemcel.
Patients who could become pregnant and patients who could father a child should use effective contraception prior to beginning mobilization through at least 6 months after administration of betibeglogene autotemcel. Effective methods of contraception include an IUD or a combination hormonal contraceptive plus barrier contraception.
Also consider precautions associated with myeloablative conditioning agents, including effects on fertility. Potential pregnancies (following treatment) should be discussed with the prescriber.
Treatment during pregnancy is not recommended. The risks of myeloablative conditioning agents on pregnancy should be considered. Potential pregnancies (following treatment) should be discussed with the prescriber.
Screen for hepatitis B virus, hepatitis C virus, human T-lymphotrophic virus 1 and 2, and HIV (1 and 2) prior to collection of cells for manufacturing. Confirm a negative HIV test prior to beginning mobilization and apheresis of CD34+ cells if antiretrovirals are required for HIV prophylaxis. Assess renal function (including CrCl) and hepatic function prior to treatment (to ensure appropriate for therapy). Monitor neutrophil counts until engraftment has been achieved. Monitor platelet counts frequently until platelet engraftment and platelet recovery are achieved; perform CBC and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. Evaluate pregnancy status prior to therapy; patients who could become pregnant should have a negative serum pregnancy test prior to beginning mobilization, prior to conditioning procedures, and prior to administering betibeglogene autotemcel.
Monitor lifelong for hematologic malignancies with a CBC (with differential) at month 6 and month 12, and then at least annually for at least 15 years after betibeglogene autotemcel treatment; perform integration site analysis at months 6, 12, and as warranted. If a malignancy occurs, contact the manufacturer (1-833-999-6378) for instructions on sample collection for testing. Monitor for signs/symptoms of hypersensitivity and/or bleeding.
Betibeglogene autotemcel is a gene therapy consisting of autologous CD34+ hematopoietic cells transduced with the BB305 lentiviral vector to add functional copies of a modified β-globin gene (Locatelli 2022). After betibeglogene autotemcel infusion, transduced CD34+ cells engraft in the bone marrow and differentiate to produce RBCs containing a modified β-globin protein (βA-T87Q-globin) to combine with α-globin and produce functional adult Hb. βA-T87Q-globin expression corrects the β/α-globin imbalance in erythroid cells of patients with β-thalassemia to increase functional adult HbA and total Hb to normal levels and eliminate dependence on RBC transfusions.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
