title: 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.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. brentjer@mskcc.org
authors.forename: Renier J
authors.initials: RJ
authors.lastname: Brentjens
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rivière
authors.forename: Jae H
authors.initials: JH
authors.lastname: Park
authors.forename: Marco L
authors.initials: ML
authors.lastname: Davila
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Wang
authors.forename: Jolanta
authors.initials: J
authors.lastname: Stefanski
authors.forename: Clare
authors.initials: C
authors.lastname: Taylor
authors.forename: Raymond
authors.initials: R
authors.lastname: Yeh
authors.forename: Shirley
authors.initials: S
authors.lastname: Bartido
authors.forename: Oriana
authors.initials: O
authors.lastname: Borquez-Ojeda
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Olszewska
authors.forename: Yvette
authors.initials: Y
authors.lastname: Bernal
authors.forename: Hollie
authors.initials: H
authors.lastname: Pegram
authors.forename: Mark
authors.initials: M
authors.lastname: Przybylowski
authors.forename: Daniel
authors.initials: D
authors.lastname: Hollyman
authors.forename: Yelena
authors.initials: Y
authors.lastname: Usachenko
authors.forename: Domenick
authors.initials: D
authors.lastname: Pirraglia
authors.forename: James
authors.initials: J
authors.lastname: Hosey
authors.forename: Elmer
authors.initials: E
authors.lastname: Santos
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Halton
authors.forename: Peter
authors.initials: P
authors.lastname: Maslak
authors.forename: David
authors.initials: D
authors.lastname: Scheinberg
authors.forename: Joseph
authors.initials: J
authors.lastname: Jurcic
authors.forename: Mark
authors.initials: M
authors.lastname: Heaney
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Mark
authors.initials: M
authors.lastname: Frattini
authors.forename: Michel
authors.initials: M
authors.lastname: Sadelain
mesh_terms: D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000276:immunology* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects* / Q000379:methods*; D015448:Leukemia, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology / Q000637:transplantation*; D014182:Transplantation, Autologous; D017211:Treatment Failure
chemical_list: D018941:Antigens, CD19