- Various studies are underway to expand the benefits and curative potential of chimeric antigen receptor (CAR) T-cell therapy to broader populations of patients with chronic lymphocytic leukemia (CLL).
Why this matters
- A small subset of patients is demonstrating >8 years of unmaintained remission following a single CAR T-cell therapy infusion.
- Review of literature in CAR T-cell therapy.
- Funding: None disclosed.
- In a trial of CAR T-cell therapy+ibrutinib in nonresponders to prior ibrutinib, 43% achieved complete remission (CR), 17/18 demonstrated morphologic CR in bone marrow, and 15/17 were minimal residual disease-negative.
- Premanufactured CAR T-cells may offer an “off the shelf” approach to shorten production and for heavily pretreated patients in whom it is challenging to harvest functional T-cells; graft-vs-host disease remains a challenge.
- CD19-directed CAR T-cells can fail when there is loss of target antigen; alternative antigenic targets/multitargeted CAR T-cells are currently being investigated.
- Other remaining challenges include:
- Methods to predict treatment response.
- Methods to prime the immune system to promote increased expansion, persistence, and potency of CAR T-cells.
- Characterization of resistance mechanisms.
- Retrospective data.