Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia Journal Article

Authors: Park, J. H.; Rivière, I.; Gonen, M.; Wang, X.; Sénéchal, B.; Curran, K. J.; Sauter, C.; Wang, Y.; Santomasso, B.; Mead, E.; Roshal, M.; Maslak, P.; Davila, M.; Brentjens, R. J.; Sadelain, M.
Article Title: Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia
Abstract: BACKGROUND CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients. METHODS We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics. RESULTS A total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden. CONCLUSIONS In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19-28z CAR T-cell infusion than was observed among patients with a higher disease burden. Copyright © 2018 Massachusetts Medical Society.
Keywords: adult; event free survival; treatment outcome; aged; middle aged; survival analysis; major clinical study; overall survival; clinical trial; mortality; neurotoxicity; follow up; follow-up studies; t lymphocyte; t-lymphocytes; metabolism; cancer immunotherapy; recurrence; acute lymphoblastic leukemia; confusion; cytokine; immunology; cytokines; receptors, antigen, t-cell; brain disease; remission; remission induction; recurrent disease; chimeric antigen receptor; precursor cell lymphoblastic leukemia-lymphoma; seizure; phase 1 clinical trial; aphasia; cd19 antigen; lymphocyte antigen receptor; leukemia remission; disorientation; cytokine release syndrome; disease burden; humans; human; priority journal; article; cd19-specific chimeric antigen receptor
Journal Title: New England Journal of Medicine
Volume: 378
Issue: 5
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2018-02-01
Start Page: 449
End Page: 459
Language: English
DOI: 10.1056/NEJMoa1709919
PUBMED: 29385376
PROVIDER: scopus
Notes: Article -- Export Date: 1 March 2018 -- Source: Scopus
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MSK Authors
  1. Renier J Brentjens
    195 Brentjens
  2. Mithat Gonen
    713 Gonen
  3. Kevin Joseph Curran
    58 Curran
  4. Jae Hong Park
    145 Park
  5. Craig Steven Sauter
    166 Sauter
  6. Michel W J Sadelain
    456 Sadelain
  7. Isabelle C Riviere
    164 Riviere
  8. Peter Maslak
    167 Maslak
  9. Xiuyan Wang
    65 Wang
  10. Mikhail Roshal
    67 Roshal
  11. Yongzeng   Wang
    12 Wang
  12. Elena   Mead
    13 Mead