The aim of this guidance is to provide education on(chimeric antigen receptor T-cell therapy (CAR T) options and considerations for effective integration of these therapies in Canadian practice, with emphasis on where CAR T fits in current paradigms, candidates for CAR T referral and post treatment monitoring and adverse event management.
This is the 1st iteration (V.1) of the CARE™ CAR T in DLBCL Guidance for 2021.
Preview of Content in Report
Primer on CAR T
Relevant Clinical Trial Highlights:
ZUMA-1. Safety and Efficacy of KTE-C19 in Adults with Refractory Aggressive Non-Hodgkin Lymphoma
JULIET. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Considerations for Integrating CAR T in Current DLBCL Practice
Which Patients are candidates for CAR T?
Specific indications include DLBCL not otherwise specified, high grade B-cell lymphoma, high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double hit by FISH), DLBCL arising from follicular lymphoma, as well as Primary mediastinal large B-cell lymphoma (PMBCL).
Early referral and timely treatment with CAR T cell therapy may improve outcomes by:
- Planning appropriate and timely bridging therapy if required to lower tumor burden
- Lessening the likelihood of having aggressive and refractory disease (relapsed rather than chemo-refractory)
- Reducing number of prior lines of therapy and increasing likelihood of having more fit T cells for CAR T manufacturing
Posttreatment Monitoring and AE Management
Acute toxicities associated with anti-CD19 CAR T cell therapy:
- CRS: characterized by fever at the onset; symptoms can be progressive and, in addition to fever, may include capillary leak/hypoxia, end organ dysfunction, and hypotension
- ICANS: toxic encephalopathy with symptoms of mild headaches, confusion, and delirium; expressive aphasia; occasional seizures; and rarely, cerebral edema; can occur in the presence or absence of systemic CRS
Late Toxicities after CD19 CAR T:
- Late neurotoxicity events including transient aphasia and seizures have occurred up to 2 months after CAR T therapy. Patients are advised not to drive or operate machinery for 8 weeks post CAR T cell therapy.
- Prolonged ≥ grade 3 cytopenias beyond day 30 observed in ~30% of patients
- B-cell aplasia occurs in almost all patients and can persist >1 year although durable remissions can be seen in patients who recover B cells
- Infections (delayed) occurred in up to 55% of patients in pivotal trials often after discharge from hospital