Version July 2025
Dosage guidance:
Safety: For autologous use only; confirm patient identity matches unique patient identifiers on the vial(s). Exagamglogene autotemcel is provided as a single dose for infusion containing a suspension of CD34+ cells in 1 or more vials; confirm correct number of vials are present (see lot information sheet provided with product shipment). Administer an antipyretic (eg, acetaminophen) and an antihistamine (eg, diphenhydramine) prior to exagamglogene autotemcel infusion.
Clinical considerations: A treatment course consists of multiple phases: 1) Plerixafor ± granulocyte-colony stimulating factor (G-CSF) mobilization and apheresis to collect CD34+ cells for manufacturing, 2) myeloablative conditioning (eg, busulfan-based), 3) exagamglogene autotemcel infusion administered after a washout period between 48 hours and 7 days after the last dose of the myeloablative conditioning.
Mobilization: Plerixafor ± G-CSF was used for mobilization in clinical trials; G-CSF should not be used in patients with sickle cell disease. A target CD34+ cell dose of ≥20 × 106 CD34+ cells/kg is recommended for product manufacture. If the minimum dose (3 × 106 CD34+ cells/kg) is not met following initial product manufacturing, the patient will require additional cycles of mobilization and apheresis, separated by ≥14 days. A collection of ≥2 × 106 CD34+ cells/kg for backup unmodified rescue cells should also be collected and cryopreserved prior to myeloablative conditioning; a third day of collection may be used to obtain the backup rescue cells.
Myeloablative conditioning preparation: Discontinue iron chelation therapy at least 7 days prior to myeloablative conditioning. Busulfan was used for myeloablative conditioning in clinical trials. Consider antiseizure prophylaxis (using agents other than phenytoin), and prophylaxis for hepatic sinusoidal syndrome (veno-occlusive disease) during treatment with busulfan. Confirm availability of autologous exagamglogene autotemcel vials at the infusion center (and availability of backup collection) prior to initiating myeloablative therapy. Refer to product labeling for further information.
Beta-thalassemia, transfusion dependent: Note: Patients should be maintained at a goal Hb ≥11 g/dL prior to apheresis and for 60 days prior to initiation of myeloablative conditioning.
IV: Minimum recommended dose: 3 × 106 CD34+ cells/kg; administer after a washout period between 48 hours and 7 days after the last dose of the myeloablative conditioning.
Sickle cell disease: Note: Patients should be maintained at a goal Hb S level <30% while maintaining total Hb ≤11 g/dL prior to apheresis and for at least 8 weeks prior to initiation of myeloablative conditioning. Discontinue disease-modifying therapy (eg, hydroxyurea, crizanlizumab, voxelotor) 8 weeks prior to the planned start of mobilization and myeloablative conditioning.
IV: Minimum recommended dose: 3 × 106 CD34+ cells/kg; administer after a washout period between 48 hours and 7 days after the last dose of the myeloablative conditioning.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl <60 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); evaluate kidney function to ensure appropriateness of exagamglogene autotemcel treatment.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); evaluate hepatic function to ensure appropriateness of exagamglogene autotemcel treatment.
Refer to adult dosing.
(For additional information see "Exagamglogene autotemcel: Pediatric drug information")
Dosage guidance:
Safety: For autologous use only; confirm patient identity matches unique patient identifiers on the vial(s). Exagamglogene autotemcel is provided as a single dose for infusion containing a suspension of CD34+ cells in 1 or more vials; confirm correct number of vials are present (see lot information sheet). Administer an antipyretic (eg, acetaminophen) and an antihistamine (eg, diphenhydramine) prior to infusion.
Clinical considerations: A treatment course consists of multiple phases: 1) Mobilization and apheresis to collect CD34+ cells for manufacturing, 2) myeloablative conditioning, and 3) exagamglogene autotemcel infusion.
Preparation for mobilization: Discontinue disease-modifying therapies for sickle cell disease (eg, hydroxyurea, crizanlizumab, voxelotor) 8 weeks before the planned start of mobilization and conditioning and/or with the initiation of red blood cell exchange or simple transfusions.
Mobilization: Plerixafor and G-CSF was used for mobilization in patients with transfusion-dependent thalassemia. Single-agent plerixafor was used for mobilization in patients with sickle cell disease; G-CSF should NOT be administered for mobilization in patients with sickle cell disease. To maximize CD34+ cell collection, 2 consecutive days of cell collection per product manufacturing cycle are recommended, if clinically tolerated. A target CD34+ cell collection is ≥20 × 106 CD34+ cells/kg. A collection and cryopreservation of ≥2 × 106 CD34+ cells/kg for back-up unmodified rescue cells is required prior to myeloablative conditioning; a third day of collection may be used to obtain the back-up rescue cells. If the minimum dose (3 × 106 CD34+ cells/kg) is not collected following 2 consecutive days of apheresis, the patient may undergo additional cycles of mobilization and apheresis, separated by ≥14 days.
Myeloablative conditioning preparation: Discontinue iron chelation therapy ≥7 days prior to myeloablative conditioning. Busulfan was used for myeloablative conditioning in clinical trials. Consider antiseizure prophylaxis (with agents other than phenytoin) and prophylaxis for hepatic sinusoidal syndrome (veno-occlusive disease) during treatment with busulfan. Confirm availability of autologous exagamglogene autotemcel and back-up cell collection at the infusion center prior to initiating myeloablative therapy. Refer to manufacturer labeling for specific protocols. Avoid the use of nonmyelosuppressive iron chelators for at least 3 months and use of myelosuppressive iron chelators for at least 6 months after exagamglogene autotemcel infusion.
Beta-thalassemia, transfusion dependent: Note: Patients should be maintained at a goal Hb ≥11 g/dL prior to apheresis and for 60 days prior to initiation of myeloablative conditioning.
Children ≥12 years and Adolescents: IV: Minimum recommended dose: 3 × 106 CD34+ cells/kg; administer after a washout period of between 48 hours and 7 days after the last dose of the myeloablative conditioning regimen.
Sickle cell disease:
Note: Patients should be maintained at a goal Hb S level <30% while maintaining total Hb ≤11 g/dL prior to apheresis and for at least 8 weeks prior to initiation of myeloablative conditioning.
Children ≥12 years and Adolescents: IV: Minimum recommended dose: 3 × 106 CD34+ cells/kg; administer after a washout period of between 48 hours and 7 days after the last dose of the myeloablative conditioning regimen.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; has not been studied in patients with eGFR <60 mL/minute/1.73 m2; evaluate patient to ensure appropriateness of therapy.
There are no dosage adjustments provided in the manufacturer's labeling; has not been studied in patients with hepatic impairment; evaluate patient to ensure appropriateness of therapy.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adolescents and adults after undergoing myeloablative conditioning.
>10%:
Dermatologic: Pruritus (grades 3/4)
Endocrine & metabolic: Hypocalcemia (grades 3/4), hypokalemia (grades 3/4)
Gastrointestinal: Abdominal pain (grades 3/4, including upper abdominal pain), cholelithiasis (grades 3/4), decreased appetite (grades 3/4), stomatitis (grades 3/4)
Hematologic & oncologic: Anemia (grades 3/4), febrile neutropenia (grades 3/4), leukopenia (grades 3/4), lymphocytopenia (grades 3/4, including decreased CD4 lymphocytes), neutropenia (grades 3/4), prolonged partial thromboplastin time (grades 3/4), thrombocytopenia (grades 3/4)
Hepatic: Hyperbilirubinemia (grades 3/4), increased gamma-glutamyl transferase (grades 3/4), increased serum alanine aminotransferase (grades 3/4)
Hypersensitivity: Infusion-related reaction
Neuromuscular & skeletal: Musculoskeletal pain (grades 3/4, including noncardiac chest pain)
Respiratory: Epistaxis (grades 3/4)
1% to 10%:
Gastrointestinal: Constipation
Hematologic & oncologic: Hemophagocytic lymphohistiocytosis
Hepatic: Hepatic sinusoidal obstruction syndrome
Infection: Sepsis, viral infection
Nervous system: Intracranial hemorrhage, pain
Respiratory: Hypoxia, oropharyngeal pain, pneumonia, upper respiratory tract infection
Miscellaneous: Fever
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Gene editing (off-target): The risk of unintended, off-target editing of individual CD34+ cells with exagamglogene autotemcel treatment cannot be ruled out due to genetic variants (effects of off-target editing are unknown). Off-target genome editing has not been observed in cells from healthy donors or patients treated with exagamglogene autotemcel.
• Hypersensitivity: Serious hypersensitivity reactions, including anaphylaxis, may occur with exagamglogene autotemcel, and are due to the dimethyl sulfoxide (DMSO) and dextran 40 components of the cryopreservative solution.
• Neutrophil engraftment failure: There is a potential risk of neutrophil engraftment failure after treatment with exagamglogene autotemcel. Neutrophil engraftment failure is defined as not achieving neutrophil engraftment (3 consecutive measurements of ANC ≥500/mm3 on 3 different days) after exagamglogene autotemcel infusion and requiring use of unmodified rescue CD34+ cells. In clinical trials, all patients achieved neutrophil engraftment (none required unmodified rescue cells); the median time to neutrophil engraftment in patients with sickle cell disease and beta-thalassemia was 27 days (range: 15 to 40 days) and 29 days (range 12 to 56 days), respectively.
• Platelet engraftment delay: Delayed platelet engraftment has been observed with exagamglogene autotemcel treatment. Platelet engraftment is defined as 3 consecutive measurements of platelets ≥50,000/mm3 (≥20,000/mm3 in beta-thalassemia) on 3 different days without administration of platelet transfusion for 7 days. In clinical trials, median time to platelet engraftment in patients with sickle cell disease and beta-thalassemia was 35 days (range: 23 to 126 days) and 44 days (range: 20 to 200 days), respectively. Bleeding risk is increased prior to platelet engraftment and until platelet engraftment is achieved; however, in clinical trials, no correlation between bleeding events and time to platelet engraftment was seen.
Disease-related concerns:
• Patients with HIV, hepatis B, or hepatitis C: Exagamglogene autotemcel has not been studied in patients with HIV-1, HIV-2, hepatis B (HBV), or hepatitis C (HCV). Exagamglogene autotemcel should not be used in patients with active HIV-1, HIV-2, HBV, or HCV.
• Prior hematopoietic cell transplant: Exagamglogene autotemcel has not been studied in patients who have received a prior autologous or allogeneic hematopoietic cell transplant. Treatment with exagamglogene autotemcel should not be used in this setting.
Concurrent drug therapy issues:
• Immunizations: Follow institutional guidelines for vaccine administration. The safety of immunization with live viral vaccines during or following exagamglogene autotemcel has not been studied.
Dosage form specific issues:
• Cryopreservative solution: Exagamglogene autotemcel contains DMSO and dextran 40, which have been associated with serious hypersensitivity reactions, including anaphylaxis.
• Universal precautions: Exagamglogene autotemcel contains genetically modified human cells; follow universal precautions and facility biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases.
Other warnings/precautions:
• Appropriate use: After exagamglogene 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 exagamglogene autotemcel infusion. If possible, avoid the use of nonmyelosuppressive iron chelators for 3 months and myelosuppressive iron chelators for 6 months after exagamglogene autotemcel infusion; restarting iron chelation after exagamglogene autotemcel 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Casgevy: (1 ea) [contains dextran 40]
No
IV: Before infusion, confirm patient identity matches unique identifiers on the exagamglogene autotemcel vial(s) (do not infuse if patient-specific label does not match).
Coordinate the timing of administration with thawing. If more than 1 vial is required, administer the contents of each vial completely before proceeding to thaw and infusing the contents of the next vial. Infuse as soon as possible after thawing; must be administered within 20 minutes after thawing.
Administer the contents of each exagamglogene autotemcel vial as an IV push through a central IV catheter; the total volume of exagamglogene administered within 1 hour should not exceed 2.6 mL/kg. Ensure all vials are administered. After infusing the contents of each vial, flush the primary line with a sufficient volume of NS to flush the tubing and the length of the IV catheter. Do not use an inline blood filter or an infusion pump.
Follow universal precautions and facility biosafety guidelines for handling and disposal.
Note: For autologous use only; confirm patient identity matches unique patient identifiers on the cassette and infusion bag(s). Exagamglogene autotemcel is provided as a single dose for infusion containing a suspension of CD34+ cells in 1 or more vials; confirm correct number of vials are present (see lot information sheet).
IV: For IV use only. Administer IV push through a central IV catheter within 20 minutes of thawing. Do not use an in-line blood filter or infusion pump when infusing exagamglogene autotemcel. The total volume administered within 1 hour should not exceed 2.6 mL/kg; do not administer via infusion pump or an in-line blood filter. After infusing the contents of each vial, flush the primary line with NS with sufficient volume to flush the tubing and the length of the IV catheter.
If more than one vial is required, administer each vial completely before thawing and administering the next vial. Ensure all vials are administered.
Follow universal precautions and facility biosafety guidelines for handling and disposal.
Beta-thalassemia, transfusion dependent: Treatment of transfusion-dependent beta-thalassemia in adults and pediatric patients ≥12 years of age.
Sickle cell disease: Treatment of sickle cell disease in adults and pediatric patients ≥12 years of age with recurrent vaso-occlusive crises.
Exagamglogene autotemcel may be confused with axicabtagene ciloleucel, betibeglogene autotemcel, brexucabtagene autoleucel, ciltacabtagene autoleucel, elivaldogene autotemcel, etranacogene dezaparvovec, idecabtagene vicleucel, lisocabtagene maraleucel, lovotibeglogene autotemcel, 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.
Crizanlizumab: May decrease therapeutic effects of Exagamglogene Autotemcel. Risk X: Avoid
Granulocyte Colony-Stimulating Factors: May increase adverse/toxic effects of Exagamglogene Autotemcel. Risk X: Avoid
Hydroxyurea: May decrease therapeutic effects of Exagamglogene Autotemcel. Risk X: Avoid
Iron Chelators: May increase myelosuppressive effects of Exagamglogene Autotemcel. Iron Chelators may decrease therapeutic effects of Exagamglogene Autotemcel. Risk X: Avoid
Luspatercept: May decrease therapeutic effects of Exagamglogene Autotemcel. Risk C: Monitor
Voxelotor: May decrease therapeutic effects of Exagamglogene Autotemcel. Risk X: Avoid
Evaluate pregnancy status prior to therapy. Patients who could become pregnant are required to have a negative serum pregnancy test prior to initiating each mobilization cycle and reconfirmed prior to myeloablative conditioning.
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 exagamglogene autotemcel.
Also consider precautions associated with myeloablative conditioning agents, including effects on fertility. Potential pregnancies (following treatment) should be discussed with the prescriber.
Animal reproduction studies have not been conducted.
The risks of myeloablative conditioning agents on pregnancy should be considered. Potential pregnancies (following treatment) should be discussed with the prescriber.
It is not known if exagamglogene autotemcel is present in breast milk.
Due to the potential for adverse events in a breastfed child, breastfeeding during myeloablative conditioning is not recommended by the manufacturer. Breastfeeding following treatment should be discussed with the prescriber.
Screen for hepatitis B virus, hepatitis C virus, and HIV (1 and 2), and any other infectious agents in accordance with local guidelines prior to collection of cells for manufacturing. Assess kidney function (including CrCl) and hepatic function prior to treatment (to ensure appropriateness for therapy). Monitor neutrophil counts until engraftment has been achieved. Monitor platelet counts frequently until platelet engraftment and platelet recovery are achieved; perform CBC and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. Evaluate pregnancy status prior to therapy; patients who could become pregnant are required to have a negative serum pregnancy test prior to initiating each mobilization cycle and reconfirmed prior to myeloablative conditioning. Monitor for signs/symptoms of hypersensitivity (during and after infusion) and/or bleeding.
Exagamglogene autotemcel is a cellular gene therapy consisting of autologous CD34+ hematopoietic cells edited by CRISPR/Cas9 technology to create a DNA double-strand break at a critical transcription binding site of the erythroid-specific enhancer region of the BCL11A gene. This modification reduces BCL11A expression in the erythroid lineage, allowing for increased γ-globin expression and fetal hemoglobin (HbF) production in erythroid cells. After exagamglogene autotemcel infusion, the edited CD34+ cells engraft in the bone marrow and differentiate to erythroid lineage cells with reduced BCL11A expression. In patients with severe sickle cell disease, HbF expression reduces intracellular hemoglobin S concentration, preventing the RBCs from sickling and addressing the underlying cause of disease, thereby eliminating vaso-occlusive crises. In transfusion-dependent beta-thalassemia, γ-globin production improves the imbalance in α-globin to non-α-globin, leading to improved erythropoiesis and increasing total Hb levels.
