CLL: broadening the scope of CAR T-cell therapy

  • Bair SM & al.
  • Am J Hematol
  • 12 Mar 2019

  • curated by David Reilly
  • Univadis Clinical Summaries
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Takeaway

  • 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.

Study design

  • Review of literature in CAR T-cell therapy.
  • Funding: None disclosed.

Key results

  • 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.

Limitations

  • Retrospective data.

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