Lyfgenia (lovotibeglogene autotemcel)

It is essential 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 lovotibeglogene autotemcel manufacturing.

Myeloablative conditioning must be administered before infusion of lovotibeglogene autotemcel. Following myeloablative conditioning, allow a minimum of 48 hours of washout before lovotibeglogene autotemcel infusion.

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

Do not sample, alter, irradiate, or refreeze lovotibeglogene autotemcel.

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

Administer lovotibeglogene autotemcel within 4 hours after thawing.

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

Dosing of lovotibeglogene autotemcel is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. The minimum recommended dose in adolescents 12 years of age or older is 3 x 106 CD34+ cells/kg.

Dosing of lovotibeglogene autotemcel is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. The minimum recommended dose is 3 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.

Lovotibeglogene Autotemcel/Anti-Retrovirals

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: Lovotibeglogene 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.

CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of lovotibeglogene autotemcel.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed.(1) There are some long-acting antiretroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.(1)

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

Lovotibeglogene Autotemcel/Disease Modifying Agents

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: The interaction potential of disease modifying agents with lovotibeglogene autotemcel is unknown.(1)

CLINICAL EFFECTS: Disease modifying agents may interfere with lovotibeglogene autotemcel therapy.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discontinue disease modifying therapies (e.g. voxelotor, crizanlizumab) for sickle cell disease at least 8 weeks prior to start of mobilization and conditioning.(1)

DISCUSSION: There is no experience with the use of disease modifying agents with lovotibeglogene autotemcel infusion.(1)

Lovotibeglogene Autotemcel/Erythropoietic Agents

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: Erythropoietic agents may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1)

CLINICAL EFFECTS: Use of erythropoietic agents before mobilization may result in unsuccessful stem cell mobilization.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discontinue erythropoietic agents at least 2 months prior to mobilization.(1)

DISCUSSION: Erythropoietic agents may interfere with the manufacturing of lovotibeglogene autotemcel therapy. There are no data regarding use of erythropoietin between apheresis and conditioning or after lovotibeglogene autotemcel therapy.(1)

Lovotibeglogene Autotemcel/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: 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 and interfere with lovotibeglogene autotemcel therapy.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discontinue hydroxyurea for at least 2 months prior to mobilization and until all cycles of apheresis are completed, and 2 days prior to conditioning.(1)

DISCUSSION: Hydroxyurea may interfere with the manufacturing and effectiveness of lovotibeglogene autotemcel therapy.(1)

Lovotibeglogene 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 lovotibeglogene 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: Iron chelators should be discontinued 7 days prior to initiation of mobilization or conditioning. Avoid myelosuppressive iron chelators for six months after lovotibeglogene autotemcel infusion. Avoid non-myelosuppressive iron chelators for three months after lovotibeglogene autotemcel infusion. If iron chelation is needed, consider phlebotomy in lieu of iron chelation when appropriate.(1)

DISCUSSION: In preparation for infusion of lovotibeglogene autotemcel, iron chelation should be discontinued 7 days prior to initiation of mobilization or conditioning.(1) In clinical trials, 60% of 45 patients experienced Grade 3 or 4 neutropenia from Day 1 to Month 24.(1)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Lovotibeglogene Autotemcel/Iron Chelators

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

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

CLINICAL EFFECTS: Iron chelators should be held prior to and after infusion with lovotibeglogene autotemcel.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Iron chelators should be discontinued 7 days prior to initiation of mobilization or conditioning. Avoid myelosuppressive iron chelators for six months after lovotibeglogene autotemcel infusion. Avoid non-myelosuppressive iron chelators for three months after lovotibeglogene autotemcel infusion. If iron chelation is needed, consider phlebotomy in lieu of iron chelation when appropriate.(1)

DISCUSSION: In preparation for infusion of lovotibeglogene autotemcel, iron chelation should be discontinued 7 days prior to initiation of mobilization or conditioning.(1)

None.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

Most common adverse reactions >= Grade 3 (incidence >= 20%) were stomatitis,thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia.

Less Frequent

• Anaphylaxis
• Bacteremia
• Sickle cell disease with crisis

Rare or Very Rare

• Acute myeloid leukemia
• Myelodysplastic syndrome

More Frequent

• Anemia
• Leukopenia
• Neutropenic disorder
• Stomatitis
• Thrombocytopenic disorder

Less Frequent

• Abnormal hepatic function tests
• Anorexia
• Fever
• Hyperbilirubinemia
• Nausea
• Pharyngitis

No enhanced messaging available.

The safety and efficacy of lovotibeglogene autotemcel have been established in pediatric patients 12 years of age and older with sickle cell disease, including 8 adolescents (age 12 years to less than 18). No clinically meaningful differences in efficacy or safety were observed between the adult and pediatric subgroups. The safety and efficacy of lovotibeglogene autotemcel in children less than 12 years of age have not been established. No data are available.

There are no available data on lovotibeglogene 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 lovotibeglogene autotemcel to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known whether lovotibeglogene autotemcel has the potential to be transferred to the fetus. Therefore, lovotibeglogene autotemcel should not be administered to women who are pregnant, and pregnancy after lovotibeglogene autotemcel infusion should be discussed with the treating physician. 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 lovotibeglogene 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 lovotibeglogene autotemcel and any potential adverse effects on the breastfed child from lovotibeglogene autotemcel. Therefore, lovotibeglogene autotemcel is not recommended for women who are breastfeeding, and breastfeeding after lovotibeglogene autotemcel infusion should be discussed with the treating physician.

Lovotibeglogene autotemcel has not been studied in patients 65 years of age and older. Autologous hematopoietic stem cell (HSC) transplantation must be appropriate for a patient to be treated with lovotibeglogene autotemcel.