Zynteglo (betibeglogene autotemcel)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

For autologous use only. For IV use only.

*Patients are required to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for betibeglogene autotemcel manufacturing.

*Full myeloablative conditioning must be administered before infusion of betibeglogene autotemcel.

*Prophylaxis for hepatic veno-occlusive disease (VOD) is recommended. Prophylaxis for seizures should be considered.

*Verify that the patient's identity matches the unique patient identification information on the betibeglogene autotemcel infusion bag(s) prior to infusion.

*Do not sample, alter, or irradiate betibeglogene autotemcel.

*Do not use an in-line blood filter or an infusion pump.

*Administer each infusion bag of betibeglogene autotemcel via IV infusion over a period of less than 30 minutes.

*See Full Prescribing Information for additional details and preparation and administration.

Dosing of betibeglogene autotemcel is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight.

The minimum recommended dose is 5.0 x 106 CD34+ cells/kg in pediatric patients older than 4 years of age. Safety and efficacy have not been established in pediatric patients younger than 4 years of age.

The minimum recommended dose is 5.0 x 106 CD34+ cells/kg.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Betibeglogene Autotemcel/Anti-Retrovirals; Hydroxyurea

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Betibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1)

CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization. Use of antiretrovirals before mobilization and apheresis may interfere with the production of betibeglogene autotemcel.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discontinue antiretrovirals and hydroxyurea for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells.

DISCUSSION: Antiretroviral medications and hydroxyurea may interfere with the manufacturing of betibeglogene autotemcel therapy.(1)

Betibeglogene Autotemcel/Myelosuppressive Iron Chelators

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Treatment with betibeglogene autotemcel requires hematopoietic stem cell (HSC) mobilization which can suppress the immune system.

CLINICAL EFFECTS: Myelosuppressive iron chelators may result in increased risk of serious infections.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid myelosuppressive iron chelators for six months after betibeglogene autotemcel infusion. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators.(1)

DISCUSSION: In clinical trials, 100% of 41 patients experienced Grade 3 or 4 neutropenia from Day 1 to Month 24.(1)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

None.

• Lactation

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

The most common non-laboratory adverse reactions (incidence >= 20%) were mucositis, febrile neutropenia, vomiting, pyrexia (fever), alopecia (hair loss), epistaxis (nose bleed), abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus (itch).

The most common Grade 3 or 4 laboratory abnormalities (> 50%) include neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia.

More Frequent

• Anemia
• Leukopenia
• Lymphopenia
• Neutropenic disorder
• Thrombocytopenic disorder

Less Frequent

• Chronic heart failure
• Dyspnea
• Hepatic veno-occlusive disease
• Hyperbilirubinemia
• Hypertension
• Hypokalemia
• Hyponatremia
• Hypophosphatemia
• Hypoxia
• Increased alanine transaminase
• Pneumonia
• Sepsis
• Viral infection

Rare or Very Rare

• Malignancy

More Frequent

• Acute abdominal pain
• Alopecia
• Constipation
• Cough
• Epistaxis
• Fever
• Headache disorder
• Musculoskeletal pain
• Nausea
• Pruritus of skin
• Stomatitis
• Vomiting

Less Frequent

• Anorexia
• Diarrhea
• Dyschromia
• Fatigue
• Hyperglycemia
• Pain in oropharynx
• Pharyngitis
• Rhinitis
• Skin rash
• Upper respiratory infection

No enhanced messaging available.

The safety and efficacy of betibeglogene autotemcel have been established in pediatric patients with beta-thalassemia requiring regular transfusions. Use of betibeglogene autotemcel is supported by two Phase 3 studies that included 27 pediatric patients in the following age groups: 16 children (less than 12 years of age) and 11 adolescents (12 years to less than 18 years of age).

No differences in efficacy or clinical safety were observed between the adult and pediatric subgroups. Engraftment times were longer in pediatric patients, but not associated with increases in infections or bleeding events. The median (min, max) time to neutrophil engraftment for patients less than 18 years was 26 (16, 39) days versus 21 (13, 27) days for patients 18 years or older. The median (min, max) time to platelet engraftment for patients less than 18 years was 50 (20, 94) days versus 43 (21, 58) days for patients 18 years or older. Longer engraftment time was associated with intact spleens.

The safety and efficacy of betibeglogene autotemcel in children less than 4 years of age have not been established. No data are available.

There are no available data with betibeglogene autotemcel 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 betibeglogene autotemcel to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known whether betibeglogene autotemcel has the potential to be transferred to the fetus. Therefore, betibeglogene autotemcel should not be administered to women who are pregnant, and pregnancy after betibeglogene autotemcel infusion should be discussed with the treating physician.

No nonclinical germline transmission studies have been conducted with betibeglogene autotemcel.

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.

There is no information regarding the presence of betibeglogene autotemcel in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for betibeglogene autotemcel and any potential adverse effects on the breastfed child from betibeglogene autotemcel. Therefore, betibeglogene autotemcel is not recommended for women who are breastfeeding, and breastfeeding after betibeglogene autotemcel infusion should be discussed with the treating physician.

Betibeglogene autotemcel has not been studied in patients >65 years of age. Hematopoietic stem cell (HSC) transplantation must be appropriate for a patient to be treated with betibeglogene autotemcel.