1. Individual has documented diagnosis of β-thalassemia by globin gene testing (Locatelli, 2022); AND

 

2. Individual requires regular peripheral blood transfusions to maintain target hemoglobin levels (Locatelli, 2022); AND

3. Individual has documented history of receiving transfusions of ≥100 ml per kilogram of body weight of packed red cells per year or who had disease that had been managed under standard thalassemia guidelines with ≥8 transfusions per year in the previous 2 years at the time of treatment decision (Locatelli, 2022); AND

4. Individual has Karnofsky performance status of ≥ 80 for adults (≥16 years of age) or a Lansky performance status of ≥ 80 for adolescents (< 16 years of age) (Locatelli, 2022); AND

5. Individual has negative serologic test for HIV infection (as per US FDA prescribing label, apheresis material from individuals with a positive test for HIV will not be accepted for betibeglogene autotemcel manufacturing) (Locatelli, 2022); AND

6. Individual does not have any of the following:

a. Availability of human leukocyte antigen-identical or human leukocyte antigen-matched donor (Locatelli, 2022); OR

b. T2*-weighted magnetic resonance imaging measurement of myocardial iron of less than 10 msec or other evidence of severe iron overload in the opinion of treating physician (Locatelli, 2022); OR

c. Advanced liver disease (meets any one of the following) (Locatelli, 2022):

i. Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value greater than 3 times the upper limit of normal; OR

ii. Baseline prothrombin time or partial thromboplastin time greater than 1.5 times the upper limit of normal; OR

iii. Magnetic resonance imaging of the liver demonstrating clear evidence of cirrhosis; OR

iv. Liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or active hepatitis; OR

d. Baseline estimated glomerular filtration rate less than 70 mL/min/1.73 square meters (FDA, 2022); OR

e. History of receiving prior gene therapy or allogenic hematopoietic stem cell transplant (Locatelli, 2022); OR

f. Any prior or current malignancy (with the exception of adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin) or myeloproliferative or significant immunodeficiency disorder (Locatelli, 2022); OR

g. Any immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome and familial adenomatous polyposis) (Locatelli, 2022); OR

h. Active, uncontrolled HCV or HBV infection (Locatelli, 2022); OR

i. Contraindication to the use of granulocyte colony stimulating factor (G-CSF), plerixafor, busulfan, or any other medicinal products required during myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients (Locatelli, 2022); OR

j. A white blood cell count less than 3 billion/L, and/or platelet count less than 100 billion/L not related to hypersplenism (Locatelli, 2022).

 

· Prophylaxis for hepatic veno-occlusive disease is recommended. Prophylaxis for seizures should be considered.

 

· Monitor platelet counts until platelet engraftment and recovery are achieved. Individuals should be monitored for thrombocytopenia and bleeding.

· Monitor absolute neutrophil counts after betibeglogene autotemcel infusion. If neutrophil engraftment does not occur administer rescue cells.

· Monitor individuals at least annually for hematologic malignancies for at least 15 years after betibeglogene autotemcel infusion.

 

· Individuals should not take prophylactic anti-retroviral medications or hydroxyurea for at least 1 month prior to mobilization or the expected duration for elimination of the medications, and until all cycles of apheresis are completed as anti-retroviral medications may interfere with manufacturing of the apheresed cells.

 

· Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. After betibeglogene autotemcel 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.

 

• Betibeglogene autotemcel is available as a single dose intravenous infusion containing a minimum of 5.0 X 10 the power of 6 CD34+cells/kg of body weight, in one or more infusion bags.

1. Individual has availability of human leukocyte antigen-identical or human leukocyte antigen-matched donor.

 

2. Individual has T2*-weighted magnetic resonance imaging measurement of myocardial iron of less than 10 msec or other evidence of severe iron overload in the opinion of treating physician.

 

3. Individual has advanced liver disease (meets any one of the following):

a. Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value greater than 3 times the upper limit of normal.

b. Baseline prothrombin time or partial thromboplastin time greater than 1.5 times the upper limit of normal.

c. Magnetic resonance imaging of the liver demonstrating clear evidence of cirrhosis.

d. Liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or active hepatitis.

 

4. Individual has baseline estimated glomerular filtration rate less than 70 mL/min/1.73 square meters.

 

5. Individual has history of receiving prior gene therapy or allogenic hematopoietic stem cell transplant.

 

6. Individual has any prior or current malignancy (with the exception of adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin) or myeloproliferative or significant immunodeficiency disorder.

 

7. Individual has any immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome and familial adenomatous polyposis).

 

8. Individual has active, uncontrolled HCV or HBV infection.

 

9. Individual has contraindication to the use of granulocyte colony stimulating factor (G-CSF), plerixafor, busulfan, or any other medicinal products required during myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.

 

10. Individual has a white blood cell count less than 3 billion/L, and/or platelet count less than 100 billion/L not related to hypersplenism.

1. Individual has availability of human leukocyte antigen-identical or human leukocyte antigen-matched donor.

 

2. Individual has T2*-weighted magnetic resonance imaging measurement of myocardial iron of less than 10 msec or other evidence of severe iron overload in the opinion of treating physician.

 

3. Individual has advanced liver disease (meets any one of the following):

a. Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value greater than 3 times the upper limit of normal.

b. Baseline prothrombin time or partial thromboplastin time greater than 1.5 times the upper limit of normal.

c. Magnetic resonance imaging of the liver demonstrating clear evidence of cirrhosis.

d. Liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or active hepatitis.

 

4. Individual has baseline estimated glomerular filtration rate less than 70 mL/min/1.73 square meters.

 

5. Individual has history of receiving prior gene therapy or allogenic hematopoietic stem cell transplant.

 

6. Individual has any prior or current malignancy (with the exception of adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin) or myeloproliferative or significant immunodeficiency disorder.

 

7. Individual has any immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome and familial adenomatous polyposis).

 

8. Individual has active, uncontrolled HCV or HBV infection.

 

9. Individual has contraindication to the use of granulocyte colony stimulating factor (G-CSF), plerixafor, busulfan, or any other medicinal products required during myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.

 

10. Individual has a white blood cell count less than 3 billion/L, and/or platelet count less than 100 billion/L not related to hypersplenism.