EFFICACY AND SAFETY OF CD19-TARGETED 19-28Z CAR MODIFIED T CELLS IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-ALL
(Abstract release date: 05/21/15)
EHA Library. Park J. 06/12/15; 103203; S112
Disclosure(s): Memorial Sloan Kettering Cancer Center
Jae H. Park
Contributions
Contributions
Abstract
Abstract: S112
Type: Oral Presentation + travel grant
Presentation during EHA20: From 12.06.2015 11:45 to 12.06.2015 12:00
Location: Room C1
Background
Adult patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) have dismal prognosis. We previously reported high anti-tumor activity of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (CAR) targeting CD19 in adult patients with ALL.
Aims
Herein, we report the long-term outcome of our phase I clinical trial in adults with R/R ALL (NCT01044069).
Methods
Adult patients with R/R B-ALL underwent leukapheresis, and T cells were transduced with a gammaretroviral vector encoding a CAR construct composed of anti-CD19 scFv linked to CD28 and CD3ζ signaling domains (19-28z). All patients received conditioning chemotherapy followed by 1–3x106 19-28z CAR T cells/kg.
Results
33 patients have been treated, and 32 patients are evaluable for response. The median age was 54 years (range, 22-74). 12 patients (36%) had Ph+ ALL, 11 patients (33%) had prior allogeneic stem cell transplant (allo-SCT), and 14 patients (42%) had ≥ 3 prior lines of therapy. At the time of CAR T cell infusion, 16 had morphologic disease (> 5% blasts in BM) and the remaining 16 patients had minimal residual disease (MRD). 13/16 patients with morphologic disease (81%) and 16/16 patients with MRD (100%) were in complete remission (CR) after 19-28z CAR T cell infusion, yielding an overall CR rate of 91% (29/32). Of the 28 MRD evaluable patients, MRD negative CR rate was 82%. 11 patients underwent allo-SCT following the CAR T cells. As of 1/25/15, the median follow-up was 5.1 months (range, 1.0-37.6+), with 14 patients having ≥6 months of follow-up. 6-month overall survival (OS) rate of all patients was 58% (95% CI: 36-74). Among the patients who achieved CR, OS rate at 6 months for patients who had allo-SCT vs. no allo-SCT following CAR T cells was 70% (95% CI: 33-89) vs. 61% (95% CI: 29-82; p=0.30). Severe cytokine release syndrome (sCRS) requiring vasopressors or mechanical ventilation for hypoxia was observed in 7 patients, effectively managed with IL-6R inhibitor and/or corticosteroids.
Summary
19-28z CAR T cells can induce a high CR rate of 91% in adult patients with R/R ALL. The risk of sCRS correlates with disease burden and can be effectively managed. These findings strongly support the use of 19-28z CAR T cells in adults with R/R ALL and warrants investigation in a phase 2 trial.
Keyword(s): Acute lymphoblastic leukemia, CD19, Cellular therapy, Gene therapy
Session topic: ALL clinical trials
Type: Oral Presentation + travel grant
Presentation during EHA20: From 12.06.2015 11:45 to 12.06.2015 12:00
Location: Room C1
Background
Adult patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) have dismal prognosis. We previously reported high anti-tumor activity of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (CAR) targeting CD19 in adult patients with ALL.
Aims
Herein, we report the long-term outcome of our phase I clinical trial in adults with R/R ALL (NCT01044069).
Methods
Adult patients with R/R B-ALL underwent leukapheresis, and T cells were transduced with a gammaretroviral vector encoding a CAR construct composed of anti-CD19 scFv linked to CD28 and CD3ζ signaling domains (19-28z). All patients received conditioning chemotherapy followed by 1–3x106 19-28z CAR T cells/kg.
Results
33 patients have been treated, and 32 patients are evaluable for response. The median age was 54 years (range, 22-74). 12 patients (36%) had Ph+ ALL, 11 patients (33%) had prior allogeneic stem cell transplant (allo-SCT), and 14 patients (42%) had ≥ 3 prior lines of therapy. At the time of CAR T cell infusion, 16 had morphologic disease (> 5% blasts in BM) and the remaining 16 patients had minimal residual disease (MRD). 13/16 patients with morphologic disease (81%) and 16/16 patients with MRD (100%) were in complete remission (CR) after 19-28z CAR T cell infusion, yielding an overall CR rate of 91% (29/32). Of the 28 MRD evaluable patients, MRD negative CR rate was 82%. 11 patients underwent allo-SCT following the CAR T cells. As of 1/25/15, the median follow-up was 5.1 months (range, 1.0-37.6+), with 14 patients having ≥6 months of follow-up. 6-month overall survival (OS) rate of all patients was 58% (95% CI: 36-74). Among the patients who achieved CR, OS rate at 6 months for patients who had allo-SCT vs. no allo-SCT following CAR T cells was 70% (95% CI: 33-89) vs. 61% (95% CI: 29-82; p=0.30). Severe cytokine release syndrome (sCRS) requiring vasopressors or mechanical ventilation for hypoxia was observed in 7 patients, effectively managed with IL-6R inhibitor and/or corticosteroids.
Summary
19-28z CAR T cells can induce a high CR rate of 91% in adult patients with R/R ALL. The risk of sCRS correlates with disease burden and can be effectively managed. These findings strongly support the use of 19-28z CAR T cells in adults with R/R ALL and warrants investigation in a phase 2 trial.
Keyword(s): Acute lymphoblastic leukemia, CD19, Cellular therapy, Gene therapy
Session topic: ALL clinical trials
Abstract: S112
Type: Oral Presentation + travel grant
Presentation during EHA20: From 12.06.2015 11:45 to 12.06.2015 12:00
Location: Room C1
Background
Adult patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) have dismal prognosis. We previously reported high anti-tumor activity of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (CAR) targeting CD19 in adult patients with ALL.
Aims
Herein, we report the long-term outcome of our phase I clinical trial in adults with R/R ALL (NCT01044069).
Methods
Adult patients with R/R B-ALL underwent leukapheresis, and T cells were transduced with a gammaretroviral vector encoding a CAR construct composed of anti-CD19 scFv linked to CD28 and CD3ζ signaling domains (19-28z). All patients received conditioning chemotherapy followed by 1–3x106 19-28z CAR T cells/kg.
Results
33 patients have been treated, and 32 patients are evaluable for response. The median age was 54 years (range, 22-74). 12 patients (36%) had Ph+ ALL, 11 patients (33%) had prior allogeneic stem cell transplant (allo-SCT), and 14 patients (42%) had ≥ 3 prior lines of therapy. At the time of CAR T cell infusion, 16 had morphologic disease (> 5% blasts in BM) and the remaining 16 patients had minimal residual disease (MRD). 13/16 patients with morphologic disease (81%) and 16/16 patients with MRD (100%) were in complete remission (CR) after 19-28z CAR T cell infusion, yielding an overall CR rate of 91% (29/32). Of the 28 MRD evaluable patients, MRD negative CR rate was 82%. 11 patients underwent allo-SCT following the CAR T cells. As of 1/25/15, the median follow-up was 5.1 months (range, 1.0-37.6+), with 14 patients having ≥6 months of follow-up. 6-month overall survival (OS) rate of all patients was 58% (95% CI: 36-74). Among the patients who achieved CR, OS rate at 6 months for patients who had allo-SCT vs. no allo-SCT following CAR T cells was 70% (95% CI: 33-89) vs. 61% (95% CI: 29-82; p=0.30). Severe cytokine release syndrome (sCRS) requiring vasopressors or mechanical ventilation for hypoxia was observed in 7 patients, effectively managed with IL-6R inhibitor and/or corticosteroids.
Summary
19-28z CAR T cells can induce a high CR rate of 91% in adult patients with R/R ALL. The risk of sCRS correlates with disease burden and can be effectively managed. These findings strongly support the use of 19-28z CAR T cells in adults with R/R ALL and warrants investigation in a phase 2 trial.
Keyword(s): Acute lymphoblastic leukemia, CD19, Cellular therapy, Gene therapy
Session topic: ALL clinical trials
Type: Oral Presentation + travel grant
Presentation during EHA20: From 12.06.2015 11:45 to 12.06.2015 12:00
Location: Room C1
Background
Adult patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) have dismal prognosis. We previously reported high anti-tumor activity of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (CAR) targeting CD19 in adult patients with ALL.
Aims
Herein, we report the long-term outcome of our phase I clinical trial in adults with R/R ALL (NCT01044069).
Methods
Adult patients with R/R B-ALL underwent leukapheresis, and T cells were transduced with a gammaretroviral vector encoding a CAR construct composed of anti-CD19 scFv linked to CD28 and CD3ζ signaling domains (19-28z). All patients received conditioning chemotherapy followed by 1–3x106 19-28z CAR T cells/kg.
Results
33 patients have been treated, and 32 patients are evaluable for response. The median age was 54 years (range, 22-74). 12 patients (36%) had Ph+ ALL, 11 patients (33%) had prior allogeneic stem cell transplant (allo-SCT), and 14 patients (42%) had ≥ 3 prior lines of therapy. At the time of CAR T cell infusion, 16 had morphologic disease (> 5% blasts in BM) and the remaining 16 patients had minimal residual disease (MRD). 13/16 patients with morphologic disease (81%) and 16/16 patients with MRD (100%) were in complete remission (CR) after 19-28z CAR T cell infusion, yielding an overall CR rate of 91% (29/32). Of the 28 MRD evaluable patients, MRD negative CR rate was 82%. 11 patients underwent allo-SCT following the CAR T cells. As of 1/25/15, the median follow-up was 5.1 months (range, 1.0-37.6+), with 14 patients having ≥6 months of follow-up. 6-month overall survival (OS) rate of all patients was 58% (95% CI: 36-74). Among the patients who achieved CR, OS rate at 6 months for patients who had allo-SCT vs. no allo-SCT following CAR T cells was 70% (95% CI: 33-89) vs. 61% (95% CI: 29-82; p=0.30). Severe cytokine release syndrome (sCRS) requiring vasopressors or mechanical ventilation for hypoxia was observed in 7 patients, effectively managed with IL-6R inhibitor and/or corticosteroids.
Summary
19-28z CAR T cells can induce a high CR rate of 91% in adult patients with R/R ALL. The risk of sCRS correlates with disease burden and can be effectively managed. These findings strongly support the use of 19-28z CAR T cells in adults with R/R ALL and warrants investigation in a phase 2 trial.
Keyword(s): Acute lymphoblastic leukemia, CD19, Cellular therapy, Gene therapy
Session topic: ALL clinical trials
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