CAR T-cell Therapy
Chimeric antigen receptor T-cell therapy:
This provides a brief overview of CAR T-cell therapy. Major complications of CAR T-cell therapy including CRS and ICANS are covered under ?sec-haeme_cris and Immune-Effector Cell-Associated Neurotoxicity Syndrome, respectively.
- Involves administration of genetically-modified autologous T-cells to target a certain malignancy
- Is a form of adoptive cellular therapy
Practice of transferring autologous or allogenic immune cells to a patient, aiming to alter their immune environment to improve response to disease.
Indications
Specific malignancies:
- Aggressive, refractory, or relapsed B-cell lymphoma
- Mantle cell lymphoma
- Multiple myeloma
Contraindications
Principles
Therapy involves:
- Apheresis of patients peripheral blood mononuclear cells
- Cryopreservation and transfer to a manufacturing facility
- Genetic modification of these cells to target a certain malignancy
- Modification occurs with addition of the Chimeric Antigen Receptor gene to the cells, generally via a viral vector
- Activation and clonal expansion of cells
- Cryopreservation and transfer back to treating institution
Entire process takes ~6 weeks. - Pre-treatment with lymphocyte-depleting chemotherapy
Improves subsequent T-cell expansion. - Re-transfusion of the modified cells
Generally via a central line to avoid extravasation. - Clonal expansion of administered cells
Genetic modifications are targeted at a particular receptor expressed by that cell. Consequently, all cells bearing this antigen will be targeted, which will include some non-malignant cells. This is known as ‘on-target, off-tumour’ toxicity.
Practice
Complications
Complications are common and may range from mild to life-threatening. They can be divided by time-course into:
CRS and ICANS are covered under ?sec-haeme_cris and Immune-Effector Cell-Associated Neurotoxicity Syndrome, respectively.
- Acute toxicity
Occurs 0-30 days after therapy:- Cytokine Release Syndrome
Severe CRS also ↑ infective risk. - Immune Effector Cell-Associated Neurotoxicity Syndrome
- Infection
- Febrile neutropenia
- Anaphylaxis
- Coagulopathy
- Thromboembolism
- Tumour Lysis Syndrome
Rare but remains a risk.
- Cytokine Release Syndrome
- Delayed toxicity
- Hypogammaglobulinaemia
- Cytopaenias
Hypogammaglobulinaemia occurs due to destruction of B-cells relating to the CD-19 targeting CAR T-cells, which results in B-cell aplasia.
Key Studies
References
- Messmer AS, Que YA, Schankin C, Banz Y, Bacher U, Novak U, et al. CAR T-cell therapy and critical care. Wien Klin Wochenschr. 2021 Dec 1;133(23):1318–25.