Obecabtagene Autoleucel – Description
- Obecabtagene autoleucel is a chimeric antigen receptor (CAR) T-cell gene therapy. It is CD19-directed immunotherapy that works by using a patient’s own genetically altered immune cells to kill B-cell cancer cells in the blood.
- Obecabtagene autoleucel is indicated for use in adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.
- Obecabtagene autoleucel has black box warnings for cytokine release syndrome, severe neurotoxicity, and new T-cell malignancies.
- Obecabtagene autoleucel was FDA-approved in November 2024.71510
Indications & Dosage
- acute lymphocytic leukemia (ALL)
Precautions
- anemia
- blood donation
- bone marrow suppression
- breast-feeding
- cytokine release syndrome
- driving or operating machinery
- encephalopathy
- fungal infection
- hepatitis
- human immunodeficiency virus (HIV) infection
- hypogammaglobulinemia
- infection
- laboratory test interference
- mental status changes
- neurotoxicity
- neutropenia
- new primary malignancy
- pregnancy
- pregnancy testing
- reproductive risk
- thrombocytopenia
- vaccination
- viral infection
Pregnancy
- Pregnancy should be avoided by females of reproductive potential during obecabtagene autoleucel treatment; pregnancy after obecabtagene autoleucel administration should be discussed with the treating physician.
- There is limited data with obecabtagene autoleucel use in pregnant women. In the FELIX study, 1 patient became pregnant 6 months following treatment and had a premature delivery at 30 weeks. It is not known if obecabtagene autoleucel has the potential to be transferred to the fetus.
- However, based on its mechanism of action, fetal toxicity including B-cell lymphocytopenia and hypogammaglobinemia may occur if the transduced cells cross the placenta.71510
Lactation
It is not known if obecabtagene autoleucel is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Consider the developmental and health benefits of breast-feeding along with the mother’s clinical need for obecabtagene autoleucel and any potential adverse effects on the breast-fed infant from obecabtagene autoleucel or from the underlying maternal condition.71510
Interactions
- Cholera Vaccine
- Dengue Tetravalent Vaccine, Live
- SARS-CoV-2 (COVID-19) vaccines
- SARS-CoV-2 Virus (COVID-19) mRNA Vaccine
- SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine
Adverse Reactions
- abdominal pain
- adrenocortical insufficiency
- anaphylactoid reactions
- anemia
- anorexia
- antibody formation
- anxiety
- aphasia
- arrhythmia exacerbation
- ascites
- bleeding
- bone marrow suppression
- chills
- coagulopathy
- confusion
- constipation
- cough
- cytokine release syndrome
- delirium
- diarrhea
- dizziness
- drowsiness
- edema
- elevated hepatic enzymes
- encephalopathy
- fatigue
- fever
- graft-versus-host disease
- headache
- heart failure
- hemophagocytic lymphohistiocytosis
- hyperferritinemia
- hypogammaglobulinemia
- hypotension
- impaired cognition
- infection
- infusion-related reactions
- insomnia
- lethargy
- leukopenia
- lymphopenia
- macrophage activation syndrome
- musculoskeletal pain
- nausea
- nephrotoxicity
- neurotoxicity
- neutropenia
- new primary malignancy
- palpitations
- pleural effusion
- posterior reversible encephalopathy syndrome
- pulmonary embolism
- rash
- seizures
- sinus tachycardia
- skin ulcer
- stomatitis
- thrombocytopenia
- thrombosis
- tremor
- visual impairment
- vomiting
- weight loss
Mechanism of Action
- Obecabtagene autoleucel is a chimeric antigen receptor (CAR) T-cell therapy that works by redirecting T-cells to target the CD19 antigen on B-cells in patients with hematologic malignancies.
- The CD3-zeta domain activates downstream signaling cascades that lead to T-cell activation. Proliferation and persistence following activation are enhanced by the presence of the 4-1BB costimulatory domain.
- The binding of CAR to CD19 activates obecabtagene autoleucel and promotes cell expansion and differentiation and triggers the lysis of CD19-expressing cells.
- This immunotherapy involves removing, genetically modifying, and then re-infusing a patient’s own T-cells.
- During the manufacturing process, the cells are genetically modified using lentiviral transduction to express a CAR comprised of a murine anti-CD19 single chain variable fragment linked to 4-IBB and CD3-zeta costimulatory domains.
- To produce CAR T-cell therapy, T-cells are collected from the blood by leukapheresis; enriched; activated; transduced with the replication incompetent lentiviral vector containing the CD19 CAR transgene; expanded in a cell culture; and then washed, formulated into a suspension, and cryopreserved.71510
References
23512.Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Department of Health and Human Services. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. Available at https://clinicalinfo.hiv.gov/guidelines/perinatal. Accessed January 6, 2025.
60092.Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014; 58: e44-100.
60871.Vaxchora (Cholera Vaccine, live, oral) package insert. Redwood City, CA: Emergent Travel Health Inc.; 2024 Jan.
64100.Dengvaxia (dengue tetravalent vaccine, live) package insert. Swiftwater, PA: Sanofi Pasteur Inc.; 2023 August.
65107.Kroger A, Bahta L, Hunter P. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). Accessed April 25, 2024. Available at https://www.cdc.gov/vaccines/hcp/imz-best-practices/?CDC_AAref_Val=https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html.
66080.Food and Drug Administration (FDA). Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization (EUA) of Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Disease 2019 (COVID-19) for 12 years and older. Purple cap and purple border. Retrieved November 22, 2022.
66526.Hauser JR, Hong H, Babady NE, et al. False-positive results for human immunodeficiency virus type 1 nucleic acid amplification testing in chimeric antigen receptor T cell therapy. J Clin Microbiol 2019;58(1):e01420-19.
69927.FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies. US Food and Drug Administration. Retrieved November 28, 2023. Available at https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous?utm_medium=email&utm_source=govdelivery.
71510.Aucatzyl (obecabtagene autoleucel) injection package insert. Gaithersburg, MD: Autolus, Inc.; 2024 Nov.
