Advances in T-cell therapy for ALL

Abstract

CD19-directed chimeric antigen receptor T cells (CART19 or CTL019) have been used with success in pediatric and adult acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL) patients. While this therapy has caused toxicities, including cytokine release syndrome and macrophage activation syndrome, these conditions are reversible with IL-6 blockade using the monoclonal antibody tocilizumab. Furthermore, 90% of the very high-risk patients who underwent infusion with CTL019 achieved a complete response, despite the fact that they previously failed multiple therapies and/or transplant. With improved cell persistence, this immunotherapy may one day prove to be more than a bridge to transplant and may in fact be a transplant alternative.

Keywords: ALL; CLL; IL-6; acute lymphocytic leukemia; chimeric antigen receptor; chronic lymphocytic leukemia; cytokine release syndrome; macrophage activation syndrome.

Copyright © 2014 Elsevier Ltd. All rights reserved.

Figures

Fig. 1

Peripheral expansion of CTL019 cells as detected by flow cytometry. CR, complete response; D, day.

Fig. 2

Lymphocyte and neutrophil reconstitution in a refractory ALL patient after CTL019. The 3 downward-facing arrows represent 3 daily CTL019 infusions at 10%, 30% and 60% of the eventual total dose.

Fig. 3

Overall survival in 30 children and adults treated with CTL019 therapy. Of this group, 5 patients who entered a CR went on to further therapy, 3 of which received an allogeneic BMT. The rest have not received further therapy to consolidate their remissions. Figure adapted from The New England Journal of Medicine; Maude SL, Frey N, Shaw PA et al., Chimeric antigen receptor T cells for sustained remissions in leukemia, Volume No 371, Page No 1510, ©2014 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.