Dosing & Uses
Dosage Forms & Strengths
cell suspension for IV infusion
- Contains minimum of 5x 106 CD34+ cells/kg (body weight) ≥1 infusion bags
- See Lot Information Sheet provided with product shipment for additional information pertaining to dose
Transfusion-dependent Beta Thalassemia
Indicated for β-thalassemia in patients who require regular red blood cell (RBC) transfusions
For autologous use only
Minimum recommended dose: 5x 106 CD34+ cells/kg as a one-time IV infusion
Provided as a single dose for infusion containing a suspension of CD34+ cells in ≥1 infusion bags
Before betibeglogene autotemcel infusion
- Before initiating mobilization, apheresis, and myeloablative conditioning, confirm that hematopoietic stem cell (HSC) transplantation is appropriate for patient
- Maintain Hgb ≥11 g/dL for at least 30 days before mobilization and 30 days before myeloablative conditioning
- In clinical trials, granulocyte-colony stimulating factor (G-CSF) and plerixafor were used for mobilization, and busulfan was used for myeloablative conditioning; refer to prescribing information for mobilization agent(s) and myeloablative conditioning agent(s) before treatment
- Screen for hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus 1 and 2 (HTLV-1/HTLV-2), and HIV-1/HIV-2, in accordance with clinical guidelines, before cell collection for manufacturing
Mobilization and apheresis
- HSC mobilization is required, followed by apheresis to obtain CD34+ cells for product manufacturing
- Target number of CD34+ cells to be collected: ≥12x 106 CD34+ cells/kg
- If minimum dose (5x 106 CD34+ cells/kg) is not met, patient may undergo additional cycles of mobilization and apheresis, separated by at least 14 days, to obtain more cells for additional manufacture
- Up to 2 drug product lots may be administered to meet target dose
- A backup collection of CD34+ cells of ≥1.5x 106 CD34+ cells/kg (if collected by apheresis) or >1x 108 TNC/kg (Total Nucleated Cells, if collected by bone marrow harvest) is required; these cells must be collected from the patient and be cryopreserved before myeloablative conditioning
-
May need backup collection for rescue treatment if there is
- Compromise of HSCs or betibeglogene autotemcel before infusion
- Primary engraftment failure
- Loss of engraftment after infusion with betibeglogene autotemcel
Myeloablative conditioning
- Full myeloablative conditioning must be administered before betibeglogene autotemcel infusion
- Consult prescribing information for myeloablative conditioning agent(s) before treatment
- Stop iron chelation at least 7 days before myeloablative conditioning
- Prophylaxis for hepatic veno-occlusive disease (VOD) recommended
- Consider prophylaxis for seizures, as appropriate
- Do not begin myeloablative conditioning until complete set of infusion bag(s) constituting the full dose of betibeglogene autotemcel received and stored at the treatment center and availability of backup collection confirmed
- After completion of the myeloablative conditioning, allow at least 48 hr of washout before betibeglogene autotemcel infusion
Dosage Modifications
Renal impairment
- Not studied
- Assess for renal impairment (ie, CrCl ≤70 mL/min/1.73 m2) to ensure HSC transplantation is appropriate
Hepatic impairment
- Not studied
- Assess for hepatic impairment to ensure HSC transplantation is appropriate
Dosing Considerations
- Not studied in patients with HIV-1, HIV-2, HTLV-1, or HTLV-2
- Negative serology test for HIV needed to ensure acceptance of apheresis material for betibeglogene autotemcel manufacturing
- Apheresis material from patients with positive HIV test will not be accepted for manufacturing
Dosage Forms & Strengths
cell suspension for IV infusion
- Contains minimum of 5x 106 CD34+ cells/kg (body weight) ≥1 infusion bags
- See Lot Information Sheet provided with product shipment for additional information pertaining to dose
Transfusion-dependent Beta Thalassemia
Indicated for β-thalassemia in patients who require regular red blood cell (RBC) transfusions
For autologous use only
Minimum recommended dose: 5x 106 CD34+ cells/kg as a one-time IV infusion
Provided as a single dose for infusion containing a suspension of CD34+ cells in ≥1 infusion bags
Before betibeglogene autotemcel infusion
- Before initiating mobilization, apheresis, and myeloablative conditioning, confirm that hematopoietic stem cell (HSC) transplantation is appropriate for patient
- Maintain Hgb ≥11 g/dL for at least 30 days before mobilization and 30 days before myeloablative conditioning
- In clinical trials, granulocyte-colony stimulating factor (G-CSF) and plerixafor were used for mobilization, and busulfan was used for myeloablative conditioning; refer to prescribing information for mobilization agent(s) and myeloablative conditioning agent(s) before treatment
- Screen for hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus 1 and 2 (HTLV-1/HTLV-2), and HIV-1/HIV-2 in accordance with clinical guidelines before cell collection for manufacturing
Mobilization and apheresis
- HSC mobilization is required, followed by apheresis to obtain CD34+ cells for product manufacturing
- Target number of CD34+ cells to be collected: ≥12x 106 CD34+ cells/kg
- If minimum dose (5x 106 CD34+ cells/kg) is not met, patient may undergo additional cycles of mobilization and apheresis, separated by at least 14 days, to obtain more cells for additional manufacture
- Up to 2 drug product lots may be administered to meet target dose
- A backup collection of CD34+ cells of ≥1.5x 106 CD34+ cells/kg (if collected by apheresis) or >1x 108 TNC/kg (Total Nucleated Cells, if collected by bone marrow harvest) is required; these cells must be collected from the patient and be cryopreserved before myeloablative conditioning
-
May need backup collection for rescue treatment if there is
- Compromise of HSCs or betibeglogene autotemcel before infusion
- Primary engraftment failure
- Loss of engraftment after infusion with betibeglogene autotemcel
Myeloablative conditioning
- Full myeloablative conditioning must be administered before betibeglogene autotemcel infusion
- Consult prescribing information for myeloablative conditioning agent(s) before treatment
- Stop iron chelation at least 7 days before myeloablative conditioning
- Prophylaxis for hepatic veno-occlusive disease (VOD) recommended
- Consider prophylaxis for seizures, as appropriate
- Do not begin myeloablative conditioning until complete set of infusion bag(s) constituting the full dose of betibeglogene autotemcel received and stored at the treatment center and availability of backup collection confirmed
- After completion of the myeloablative conditioning, allow at least 48 hr of washout before betibeglogene autotemcel infusion
Dosage Modifications
Renal impairment
- Not studied
- Assess for renal impairment (ie, CrCl ≤70 mL/min/1.73 m2) to ensure HSC transplantation is appropriate
Hepatic impairment
- Not studied
- Assess for hepatic impairment to ensure HSC transplantation is appropriate
Dosing Considerations
- Not studied in patients with HIV-1, HIV-2, HTLV-1, or HTLV-2
- Negative serology test for HIV needed to ensure acceptance of apheresis material for betibeglogene autotemcel manufacturing
- Apheresis material from patients with positive HIV test will not be accepted for manufacturing
Not studied in patients aged >65 years
Hematopoietic stem cell (HSC) transplantation must be appropriate for patient to be treated with betibeglogene autotemcel
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (36)
- abacavir
abacavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- atazanavir
atazanavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- bictegravir
bictegravir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- cabotegravir
cabotegravir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- dapivirine intravaginal
dapivirine intravaginal, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- darunavir
darunavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- deferasirox
betibeglogene autotemcel increases effects of deferasirox by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Discontinue iron chelators at least 7 days before starting conditioning. Some iron chelators are myelosuppressive. After infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of nonmyelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate.
- deferiprone
betibeglogene autotemcel increases effects of deferiprone by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Discontinue iron chelators at least 7 days before starting conditioning. Some iron chelators are myelosuppressive. After infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of nonmyelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate.
- deferoxamine
betibeglogene autotemcel increases effects of deferoxamine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Discontinue iron chelators at least 7 days before starting conditioning. Some iron chelators are myelosuppressive. After infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of nonmyelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate.
- delavirdine
delavirdine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- didanosine
didanosine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- dolutegravir
dolutegravir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- doravirine
doravirine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- efavirenz
efavirenz, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- elvitegravir
elvitegravir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- emtricitabine
emtricitabine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- enfuvirtide
enfuvirtide, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- etravirine
etravirine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- fosamprenavir
fosamprenavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- fostemsavir
fostemsavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- hydroxyurea
hydroxyurea, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take hydroxyurea for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. .
- ibalizumab
ibalizumab, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- indinavir
indinavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- lamivudine
lamivudine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- maraviroc
maraviroc, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- nelfinavir
nelfinavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- nevirapine
nevirapine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- raltegravir
raltegravir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- rilpivirine
rilpivirine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- ritonavir
ritonavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- saquinavir
saquinavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- stavudine
stavudine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- tenofovir DF
tenofovir DF, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- tipranavir
tipranavir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- zidovudine
zidovudine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
Monitor Closely (20)
- adenovirus types 4 and 7 live, oral
betibeglogene autotemcel, adenovirus types 4 and 7 live, oral. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- BCG vaccine live
betibeglogene autotemcel, BCG vaccine live. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- cholera vaccine
betibeglogene autotemcel, cholera vaccine. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- dengue vaccine
betibeglogene autotemcel, dengue vaccine. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- Ebola Zaire vaccine
betibeglogene autotemcel, Ebola Zaire vaccine. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- influenza virus vaccine quadrivalent, intranasal
betibeglogene autotemcel, influenza virus vaccine quadrivalent, intranasal. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- measles (rubeola) vaccine
betibeglogene autotemcel, measles (rubeola) vaccine. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- measles mumps and rubella vaccine, live
betibeglogene autotemcel, measles mumps and rubella vaccine, live. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- measles, mumps, rubella and varicella vaccine, live
betibeglogene autotemcel, measles, mumps, rubella and varicella vaccine, live. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- poliovirus vaccine live oral trivalent
betibeglogene autotemcel, poliovirus vaccine live oral trivalent. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- rotavirus oral vaccine, live
betibeglogene autotemcel, rotavirus oral vaccine, live. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- rubella vaccine
betibeglogene autotemcel, rubella vaccine. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- smallpox (vaccinia) and monkeypox vaccine, live, nonreplicating
betibeglogene autotemcel, smallpox (vaccinia) vaccine, attenuated. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- smallpox (vaccinia) vaccine, attenuated
betibeglogene autotemcel, smallpox (vaccinia) vaccine, attenuated. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- smallpox (vaccinia) vaccine, live
betibeglogene autotemcel, smallpox (vaccinia) vaccine, live. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- typhoid polysaccharide vaccine
betibeglogene autotemcel, typhoid polysaccharide vaccine. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- typhoid vaccine live
betibeglogene autotemcel, typhoid vaccine live. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- varicella virus vaccine live
betibeglogene autotemcel, varicella virus vaccine live. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- yellow fever vaccine
betibeglogene autotemcel, yellow fever vaccine. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
- zoster vaccine live
betibeglogene autotemcel, zoster vaccine live. Other (see comment). Use Caution/Monitor. Comment: Follow institutional guidelines for vaccine administration. Safety of live vaccines during or following treatment not studied. .
Minor (0)
Adverse Effects
>10%
Any grade
- Mucositis (95%)
- Febrile neutropenia (51%)
- Vomiting (49%)
- Pyrexia (49%)
- Alopecia (44%)
- Epistaxis (42%)
- Abdominal pain (39%)
- Musculoskeletal pain (37%)
- Cough (34%)
- Headache (29%)
- Diarrhea (27%)
- Rash (27%)
- Nausea (24%)
- Constipation (24%)
- Decreased appetite (24%)
- Pigment disorder (24%)
- Pruritus (22%)
- Viral infection (17%)
- Procedural pain (15%)
- Transfusion reaction (15%)
- Oropharyngeal pain (15%)
- Nasopharyngitis (12%)
- Fatigue (12%)
- Dyspnea (12%)
- Hypoxia (12%)
- Rhinitis (12%)
Grade ≥3
- Neutropenia (100%)
- Thrombocytopenia (100%)
- Leukopenia (100%)
- Anemia (95%)
- Mucositis (63%)
- Lymphopenia (61%)
- Febrile neutropenia (51%)
- ALT increased (24%)
- Hypophosphatemia (20%)
- Epistaxis (20%)
- Decreased appetite (15%)
- Hyperglycemia (14%)
- Hypokalemia (12%)
- Pyrexia (12%)
1-10%
Any grade
- Dyspepsia (10%)
- Gingival bleeding (10%)
- Hypertension (10%)
- Sepsis (10%)
- Veno-occlusive liver disease (10%)
Grade ≥3
- Hyperbilirubinemia (10%)
- Hyponatremia (10%)
- Sepsis (10%)
- Hypoxia (7%)
- Veno-occlusive liver disease (7%)
- Dyspepsia (5%)
- Gingival bleeding (2%)
- Viral infection (2%)
- Nausea (2%)
- Abdominal pain (2%)
Other
- Infections and infestations: Pneumonia (7%)
- Infusion-related reactions: Abdominal pain (7%), tachycardia (2%)
- Cardiac disorders: Congestive heart failure (2%)
Warnings
Contraindications
None
Cautions
Delayed platelet engraftment
- Delayed platelet engraftment observed
- Bleeding risk increased before platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% incidence of decreased platelets Grade ≥3 on or after Day 100
- Counsel patients on bleeding risk until platelet recovery achieved; instruct patients to seek immediate attention for new or worsening bleeding or bruising
- Monitor for thrombocytopenia and bleeding according to standard guidelines
- Conduct frequent platelet counts until platelet engraftment and platelet recovery achieved
- Perform complete blood count (CBC) determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise
Risk of neutrophil engraftment failure
- Potential risk for neutrophil engraftment failure after treatment
- Neutrophil engraftment failure defined as failure to achieve 3 consecutive absolute neutrophil counts (ANCs) ≥500 cells/μL obtained on different days by Day 43 after infusion
- Monitor neutrophil counts until engraftment achieved
- If neutrophil engraftment failure occurs, provide rescue treatment with the backup collection of CD34+ cells
Risk of insertional oncogenesis
- Potential risk of lentiviral vector (LVV)–mediated insertional oncogenesis after treatment
- Patients may develop hematologic malignancies and should be monitored lifelong
- Monitor for hematologic malignancies with CBC (with differential) at 6 and 12 months and then at least annually for ≥15 years after treatment, and integration site analysis at 6 and 12 months and as warranted
- If malignancy occurs, contact bluebird bio at 1-833-999-6378 for reporting and to obtain instructions on collection of samples for testing
Hypersensitivity reactions
- Allergic reactions, including anaphylaxis, may occur
- Cell suspension contains dimethyl sulfoxide (DMSO)
Interference with serology testing
- Patients who have received betibeglogene autotemcel are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV
- Use alternate test
Drug interaction overview
-
Vaccines
- Follow institutional guidelines for vaccine administration
- Safety of immunization with live viral vaccines during or following betibeglogene autotemcel treatment has not been studied
-
Antiretrovirals and hydroxyurea
- Do not take antiretrovirals or hydroxyurea for at least 1 month before mobilization or the expected duration for elimination of the medications, and until all cycles of apheresis are completed
- Antiretrovirals may interfere with manufacturing of the apheresed cells
-
Iron chelation
- Consider drug-drug interactions between iron chelators and myeloablative conditioning agent
- Discontinue iron chelators at least 7 days before starting conditioning
- Consult prescribing information for iron chelator(s) and the myeloablative conditioning agent for recommendations regarding coadministration with CYP3A substrates
- Some iron chelators are myelosuppressive; after betibeglogene autotemcel infusion, avoid use of these iron chelators for 6 months
- If iron chelation needed, consider administration of non-myelosuppressive iron chelators
- Phlebotomy can be used in lieu of iron chelation, when appropriate
-
Erythropoiesis-stimulating agents
- No information available regarding coadministration of erythropoiesis-stimulating agents with betibeglogene autotemcel
Pregnancy & Lactation
Pregnancy
Confirm negative serum pregnancy test before start of mobilization and reconfirm before conditioning procedures and before betibeglogene autotemcel administration
Data are not available regarding administration in pregnant females; consider risks to pregnancy and fertility associated with myeloablative conditioning agents
No reproductive and developmental toxicity studies in animals have been conducted
Contraception
- Data are insufficient to provide recommendation on duration of contraception following treatment
- Females of childbearing potential and males capable of fathering a child: Use effective contraception (ie, IUD or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration
- Advise patients of risks associated with conditioning agents
Infertility
- Data are unavailable regarding effects on fertility
- Data are available on infertility risk of myeloablative conditioning
- Advise patients of option to cryopreserve semen or ova before treatment, if appropriate
Lactation
Data are not available regarding presence in human milk, effect on breastfed infants, and effects on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Gene therapy that adds functional copies of a modified beta-globin gene into the patients’ hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with BB305 lentiviral vector (LVV), thereby addressing the underlying genetic cause of β-thalassemia
After infusion, transduced CD34+ HSCs engraft in bone marrow and differentiate to produce RBCs containing biologically active beta A-T87Q-globin (a modified beta-globin protein) that combines with alpha globin to produce functional hemoglobin containing beta A-T87Q-globin (HbA-T87Q)
Administration
IV Preparation
Coordinate timing of thawing betibeglogene autotemcel and infusion
Confirm infusion time in advance and adjust start time of thaw such that betibeglogene autotemcel will be available for infusion when the patient and healthcare providers are ready
Steps for thawing
- Remove each metal cassette from liquid nitrogen storage and remove each infusion bag from metal cassette
- Confirm that betibeglogene autotemcel (Zynteglo) is printed on infusion bag(s)
- Confirm patient identity matches unique patient identifiers located on betibeglogene autotemcel infusion bag(s); do not infuse if information on the patient-specific label on the infusion bag does not match the intended patient, and contact bluebird bio at 1-833-999-6378
- Ensure correct number of infusion bags are present; use accompanying Lot Information Sheet to confirm each infusion bag is within expiration date
- Inspect each infusion bag for any breaches of integrity before thawing and infusion; if compromised, follow local guidelines and contact bluebird bio immediately at 1-833-999-6378
- If >1 infusion bag provided, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag
- Thaw at 37ºC (98.6ºF) in water bath or dry bath; thawing of each infusion bag takes ~2-4 minutes; do not leave betibeglogene autotemcel unattended; do not submerge infusion ports in water bath
- After thaw, mix contents gently by massaging infusion bag to disperse clumps of cellular material until all of contents are uniform; if visible cell clumps remain, continue to gently mix contents in bag; most small clumps of cellular material should disperse with gentle manual mixing; do not filter, wash, spin down and/or resuspend in new media before infusion
- Do not sample, alter, irradiate, or refreeze
IV Administration
For autologous use only; patient’s identity must match the patient identifiers on the betibeglogene autotemcel cassette(s) and infusion bag(s); do not infuse if information on label does not match intended patient
Product must be administered within 4 hr after thawing
Do not use an in-line blood filter or infusion pump
Infusion steps
- Expose sterile port on infusion bag by tearing off the protective wrap covering port
- Access infusion bag and infuse betibeglogene autotemcel as soon as possible after thawing; complete infusion within 4 hr once thawed
- Administer each infusion bag via IV infusion over <30 minutes; if >1 infusion bag is provided, administer each infusion bag completely before proceeding to thaw and infuse next infusion bag
- Flush all betibeglogene autotemcel remaining in infusion bag(s) and any associated tubing with ≥50 mL 0.9% NaCl to ensure that as many cells as possible are infused into the patient
After betibeglogene autotemcel administration
- Follow standard procedures for patient management after HSC transplantation
- Irradiate any blood products required within first 3 months after infusion
- G-CSF not recommended for 21 days after infusion
- Restarting iron chelation after infusion may be necessary and should be based on clinical practice; 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
Storage
Betibeglogene autotemcel is shipped to the treatment center in the vapor phase of liquid nitrogen shipper
Confirm patient identifiers on product label(s) and Lot Information Sheet within the shipper
If there are any concerns about the product or packaging upon receipt, contact bluebird bio at 1-833-999-6378
Keep the infusion bag(s) in metal cassette(s), and transfer betibeglogene autotemcel from the vapor phase of liquid nitrogen shipper to treatment center vapor phase of liquid nitrogen storage at ≤ -140ºC (≤ -220ºF)
Store in the vapor phase of liquid nitrogen at ≤ -140ºC (≤ -220ºF) until ready for thaw and administration
Contains human blood cells that are genetically modified with replication-incompetent, self-inactivating lentiviral vector (LVV); follow universal precautions and biosafety guidelines (Biosafety Level 2) for handling and disposal to avoid potential transmission of infectious diseases
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
