Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias.

Abstract

We report the findings from the first 10 patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) or relapsed B-cell acute lymphoblastic leukemia (ALL) we have enrolled for treatment with autologous T cells modified to express 19-28z, a second-generation chimeric antigen (Ag) receptor specific to the B-cell lineage Ag CD19. Eight of the 9 treated patients tolerated 19-28z(+) T-cell infusions well. Three of 4 evaluable patients with bulky CLL who received prior conditioning with cyclophosphamide exhibited either a significant reduction or a mixed response in lymphadenopathy without concomitant development of B-cell aplasia. In contrast, one patient with relapsed ALL who was treated in remission with a similar T-cell dose developed a predicted B-cell aplasia. The short-term persistence of infused T cells was enhanced by prior cyclophosphamide administration and inversely proportional to the peripheral blood tumor burden. Further analyses showed rapid trafficking of modified T cells to tumor and retained ex vivo cytotoxic potential of CD19-targeted T cells retrieved 8 days after infusion. We conclude that this adoptive T-cell approach is promising and more likely to show clinical benefit in the setting of prior conditioning chemotherapy and low tumor burden or minimal residual disease. These studies are registered at www.clinicaltrials.org as #NCT00466531 (CLL protocol) and #NCT01044069 (B-ALL protocol).

• Authors: Renier J Brentjens, Isabelle Rivière, Jae H Park, Marco L Davila, Xiuyan Wang, Jolanta Stefanski, Clare Taylor, Raymond Yeh, Shirley Bartido, Oriana Borquez-Ojeda, Malgorzata Olszewska, Yvette Bernal, Hollie Pegram, Mark Przybylowski, Daniel Hollyman, Yelena Usachenko, Domenick Pirraglia, James Hosey, Elmer Santos, Elizabeth Halton, Peter Maslak, David Scheinberg, Joseph Jurcic, Mark Heaney, Glenn Heller, Mark Frattini, Michel Sadelain
• Journal: Blood (Blood) Vol. 118 Issue 18 Pg. 4817-28 (Nov 03 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21849486 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD19

Topics

• Adult
• Aged
• Antigens, CD19 (immunology, metabolism)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Drug Resistance, Neoplasm (physiology)
• Female
• Graft Survival (physiology)
• Humans
• Immunotherapy, Adoptive (adverse effects, methods)
• Leukemia, B-Cell (drug therapy, immunology, therapy)
• Male
• Middle Aged
• Recurrence
• T-Lymphocytes (immunology, metabolism, physiology, transplantation)
• Transplantation, Autologous
• Treatment Failure