IMPACT OF DISEASE BURDEN ON LONG-TERM OUTCOME OF CD19-TARGETED CAR MODIFIED T CELLS IN ADULT PATIENTS WITH RELAPSED B-ALL
Author(s): ,
Jae Park
Affiliations:
MEMORIAL SLOAN-KETTERING CANCER CENTER,New York,United States
,
Isabelle Riviere
Affiliations:
MEMORIAL SLOAN-KETTERING CANCER CENTER,New York,United States
,
Xiuyan Wang
Affiliations:
MEMORIAL SLOAN-KETTERING CANCER CENTER,New York,United States
,
Michel Sadelain
Affiliations:
MEMORIAL SLOAN-KETTERING CANCER CENTER,New York,United States
Renier Brentjens
Affiliations:
MEMORIAL SLOAN-KETTERING CANCER CENTER,New York,United States
EHA Learning Center. Park J. Jun 11, 2016; 135254
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Abstract
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Abstract: S498

Type: Oral Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45

Location: Auditorium 2

Background
We have previously reported high response rates in adult patients with relapsed or refractory (R/R) B-cell ALL following CD19-targeted 19-28z chimeric antigen receptor (CAR) modified T cells regardless of the disease burden at the time of T cell infusion.  However, the impact of disease burden on toxicity and long-term clinical outcome in patients who received 19-28z CAR modified T cells has not been examined in detail.

Aims
In order to better understand the association between pre-treatment disease burden and tolerability and long-term efficacy of 19-28z CAR T cells, herein we report the result of of a focused analysis from the phase I clinical trial of 19-28 CAR T cells in adults patients with R/R B-ALL (NCT01044069).

Methods
Adult patients with R/R B-ALL were enrolled to the phase I clinical trial.  All patients underwent bone marrow (BM) biopsy immediately prior to 19-28z CAR T cell infusion, and were divided into two cohorts based on the blast % in BM: minimal disease (<5% blasts) vs. morphologic disease (≥ 5% blasts).  Subsequently, patients received lymphodepleting chemotherapy followed by 19-28z CAR T cell infusion. 

Results
Of 46 patients treated, 21 patients had minimal disease and 25 patients had morphologic disease at the time of CAR T cell infusion.  Baseline disease and treatment characteristics were similar between the two cohorts, except less HSCT in the minimal disease cohort (29 vs. 48%). Complete response (CR) and minimal residual disease-negative CR (MRD-CR) rates were 91% and 71% in the minimal disease cohort, and 75% and 65% in the morphologic disease cohort, respectively.  Severe cytokine release syndrome exclusively occurred in patients with morphologic disease (44% vs. 0%) but grade 3/4 neurotoxicity was observed in 14% of patients with minimal disease vs. 40% with morphologic disease.  Although overall relapse rates did not differ between the two cohorts, no relapse or death occurred in the minimal disease cohort beyond 12 months. At a median follow-up of 12.0 months (range, 1-45), the estimated 6-month overall survival (OS) rates for all patients in the minimal disease and morphologic disease cohorts were 73% and 57%, respectively. Among the patients who achieved MRD-CR, the estimated 6-month OS rates were 92% for the minimal disease cohort with remissions extending beyond 3 years, and 65% for the morphologic disease cohort.   

Conclusion
These data confirm the potent anti-tumor efficacy of 19-28z CAR T cells (JCAR015) in adult patients with R/R ALL regardless of pre-treatment disease burden.  Patients with minimal disease appear to have more favorable toxicity profile and long-term survival rates.  These findings support the use of 19-28z CAR T cells in earlier lines of ALL treatment, such as in a frontline setting.  

Session topic: Acute lymphoblastic leukemia - Clinical

Keyword(s): ALL, CD19, Cellular therapy, Immunotherapy
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