Version October 2024
Dosage guidance:
Safety: For autologous use only; confirm patient identity matches unique patient identifiers on the infusion bag(s) and lot information sheet. Atidarsagene autotemcel is provided as a single dose for infusion containing a suspension of CD34+ cells in 1 to 8 infusion bag(s); confirm correct number of infusion bags to be administered are present (see lot information sheet provided with product shipment).
Dosage form information: Each infusion bag contains 10 to 20 mL of atidarsagene autotemcel with 2 to 11.8 × 106 CD34+ cells/mL suspended in cryopreservation solution.
Clinical considerations: A treatment course consists of multiple phases: 1) mobilization, 2) apheresis, 3) busulfan myeloablative conditioning, and 4) atidarsagene autotemcel infusion, with a minimum of 24 hours washout between busulfan and atidarsagene autotemcel infusion.
Mobilization and apheresis: Hematopoietic stem cell (HSC) mobilization followed by apheresis is required; in clinical trials, granulocyte colony-stimulating factor (G-CSF) with or without plerixafor was used for mobilization. A collection of ≥8 × 106 CD34+ cells/kg of autologous cells is recommended. If the minimum dose (8 × 106 CD34+ cells/kg) is not met, the patient may undergo additional cycles of mobilization. An unmanipulated back-up collection of ≥2 × 106 CD34+ cells/kg for rescue treatment should be cryopreserved prior to myeloablative conditioning.
Myeloablative conditioning: Myeloablative conditioning is required before atidarsagene autotemcel is administered. Busulfan was used in clinical trials; use of alternative conditioning agents is not supported (no data). Confirm availability of autologous atidarsagene autotemcel and back-up cell collection at the infusion center prior to initiating myeloablative conditioning therapy. Refer to manufacturer's labeling for details.
Metachromatic leukodystrophy, treatment: Note: Administer after a washout period of at least 24 hours after completion of myeloablative conditioning.
Infants ≥8 months and Children:
Presymptomatic late infantile: IV infusion: Minimum dose: 4.2 × 106 CD34+ cells/kg as a single dose; maximum dose: 30 × 106 CD34+ cells/kg.
Presymptomatic early juvenile: IV infusion: Minimum dose: 9 × 106 CD34+ cells/kg as a single dose; maximum dose: 30 × 106 CD34+ cells/kg.
Early symptomatic early juvenile: IV infusion: Minimum dose: 6.6 × 106 CD34+ cells/kg as a single dose; maximum dose: 30 × 106 CD34+ cells/kg.
There are no dosage adjustments provided in the manufacturer's labeling; has not been studied in patients with kidney impairment.
There are no dosage adjustments provided in the manufacturer's labeling; has not been studied in patients with liver impairment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for infants and children.
>10%:
Dermatologic: Skin rash (33%)
Gastrointestinal: Gastroenteritis (21%), stomatitis (77%)
Hematologic & oncologic: Blood coagulation test abnormality (elevated levels of D-dimer: 67%), febrile neutropenia (85%), neutropenia (28%)
Hepatic: Hepatomegaly (18%), increased liver enzymes (23%; including increased serum alanine aminotransferase [grade 3: 3%], increased serum aspartate aminotransferase [grade 3: 3%])
Immunologic: Antibody development (15%)
Infection: Serious infection (grade 3: 39%; including bacterial infection, fungal infection, and viral infection), viral infection (28%)
Respiratory: Respiratory tract infection (54%)
Miscellaneous: Fever (21%)
1% to 10%:
Hematologic & oncologic: Anemia (8%), platelet disorder (delayed platelet engraftment: 10%)
Hepatic: Hepatic sinusoidal obstruction syndrome (8%)
Frequency not defined: Nervous system: Encephalitis
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Encephalitis: Increased risk of encephalitis may occur with atidarsagene autotemcel treatment; may trigger relapsing remitting pattern of encephalitis disease progression.
• Hypersensitivity: Allergic reactions may occur with atidarsagene autotemcel. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) component.
• Infection: Serious infections occurred in patients after atidarsagene autotemcel infusion, including grade 3 infections. Viral, bacterial, fungal, and unspecified infections were reported. Neutropenic fever has been observed within 1 month after atidarsagene autotemcel infusion.
• Insertional oncogenesis: There is a potential risk of lentiviral vector-mediated insertional oncogenesis following treatment with atidarsagene autotemcel. Patients may develop hematologic malignancies and should be monitored lifelong. If a malignancy occurs, contact the manufacturer (1-888-878-0185) 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 atidarsagene autotemcel. Neutrophil engraftment failure is defined as failure to achieve 3 consecutive ANCs ≥500/mm3 obtained on different days by day 60 after atidarsagene autotemcel infusion. If neutrophil engraftment failure occurs in a patient treated with atidarsagene autotemcel, provide rescue treatment with the backup collection of CD34+ cells.
• Platelet engraftment delay: Delayed platelet engraftment has been observed with atidarsagene autotemcel treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia. Platelet engraftment delay has been observed after day 60 and may require platelet transfusions. Patients should be made aware of the risk of bleeding until platelet recovery has been achieved.
• Thromboembolic events: Increased risk of thrombosis and thromboembolic events may occur with atidarsagene autotemcel treatment. Evaluate patients for thrombosis risk factors; antithrombotic prophylaxis was used in some patients.
• Veno-occlusive disease: Development of veno-occlusive disease occurred during clinical trials, including grade 3 and 4; consider antithrombotic prophylaxis agents in patients at increased risk for veno-occlusive disease.
Disease-related concerns:
• Patients with HIV: Antiretroviral medications are not recommended within at least 1 month prior to mobilization or the expected duration needed for the elimination of the medications; may interfere with manufacturing of the apheresed cells. Delay mobilization and apheresis of CD34+ cells in patients requiring antiretroviral prophylaxis until HIV infection is ruled out.
Other warnings/precautions:
• Appropriate use: After atidarsagene 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 atidarsagene autotemcel infusion. Patients should not donate blood, organs, tissues, or cells at any time in the future.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Lenmeldy: (1 ea)
No
Note: For autologous use only; confirm patient identity matches unique patient identifiers on the infusion bag(s) and lot information sheet. Atidarsagene autotemcel is provided as a single dose for infusion containing a suspension of CD34+ cells in 1 to 8 infusion bag(s); confirm correct number of infusion bags to be administered are present (see lot information sheet provided with product shipment).
IV: For IV use only. Calculated infusion rate based on volume in each infusion bag; infuse each infusion bag over <2 hours. If more than one infusion bag needed, do not infuse more than one bag per hour. Do not use a leukodepleting filter. See manufacturer labeling for more information. After infusing each bag, flush all remaining atidarsagene autotemcel remaining in infusion bag and any associated tubing with NS using a rinse volume that is equal to or greater than the priming volume of any IV infusion set used to ensure that as many cells as possible are infused.
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 2 hours after thawing.
Keep the infusion bag(s) in the metal cassette(s) and store/transfer in the vapor phase of liquid nitrogen at <−130°C (<−202°F) until ready for thaw and administration. Thaw prior to infusion. Do not refreeze after thawing. Do not irradiate, as this could lead to inactivation. Product must be completely administered within 2 hours after thawing. Contact manufacturer (1-888-878-0185) with any concerns about product or packaging upon receipt.
Treatment of presymptomatic late infantile metachromatic leukodystrophy; treatment of presymptomatic early juvenile metachromatic leukodystrophy; treatment of early symptomatic early juvenile metachromatic leukodystrophy (All indications: FDA approved in pediatric patients [age not specified]).
Atidarsagene autotemcel may be confused with axicabtagene ciloleucel, betibeglogene autotemcel, 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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
Antiretroviral Agents: May diminish the therapeutic effect of Atidarsagene Autotemcel. Risk X: Avoid combination
Vaccines: Atidarsagene Autotemcel may enhance the adverse/toxic effect of Vaccines. Atidarsagene Autotemcel may diminish the therapeutic effect of Vaccines. Risk X: Avoid combination
Patients who could become pregnant are required to have a negative serum pregnancy test prior to initiating the mobilization cycle and reconfirmed prior to myeloablative conditioning and prior to the administration of atidarsagene autotemcel.
Patients who could become pregnant and patients with a partner who could become pregnant should use effective contraception prior to beginning mobilization through at least 6 months after administration of atidarsagene autotemcel.
Consider precautions associated with myeloablative conditioning agents, including effects on fertility and fertility preservation, if appropriate.
Reproduction studies have not been conducted.
Do not administer during pregnancy due to the risks of myeloablative conditioning. Pregnancies following atidarsagene autotemcel should be discussed with the treating physician.
Prior to treatment: Screen for hepatitis B virus, hepatitis C virus, human T-lymphotrophic virus 1 and 2, HIV 1 and 2, cytomegalovirus, and mycoplasma infection. Assess kidney function and liver function (to ensure appropriate for therapy). Evaluate pregnancy status; patients who could become pregnant should have a negative serum pregnancy test prior to beginning mobilization, prior to conditioning procedures, and prior to administering atidarsagene autotemcel. Evaluate risk factors for thrombosis.
Following treatment: Monitor LFTs and signs and symptoms of veno-occlusive disease for 1 month after atidarsagene autotemcel treatment. Monitor neutrophil count until engraftment is achieved. Monitor platelet count frequently until platelet engraftment and platelet recovery are achieved. Monitor for signs and symptoms of infection, bleeding, hypersensitivity, and/or encephalitis. Evaluate risk factors for thrombosis.
Monitor lifelong for hematologic malignancies with a CBC (with differential) annually for at least 15 years after atidarsagene autotemcel treatment; perform integration site analysis as warranted for at least 15 years after atidarsagene autotemcel treatment.
Atidarsagene autotemcel is a gene therapy consisting of autologous CD34+ hematopoietic cells transduced with a lentiviral vector encoding the human arylsulfatase A (ARSA) gene to add functional copies of the ARSA cDNA into the hematopoietic stem cells. After atidarsagene autotemcel infusion, transduced CD34+ hematopoietic stem cells engraft in the bone marrow and repopulate the hematopoietic compartment and their progeny produce ARSA enzyme. Functional ARSA breaks down or prevents the harmful accumulation of sulfatides.
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