DURABLE REMISSIONS AFTER MONOTHERAPY WITH CD19-SPECIFIC CHIMERIC ANTIGEN RECEPTOR (CAR)-MODIFIED T CELLS IN CHILDREN AND YOUNG ADULTS WITH RELAPSED/REFRACTORY ALL
(Abstract release date: 05/19/16)
EHA Library. Maude S. 06/11/16; 135253; S497
Dr. Shannon Maude
Contributions
Contributions
Abstract
Abstract: S497
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Auditorium 2
Background
Targeted immunotherapy with chimeric antigen receptor (CAR)-modified T cells can produce potent anti-tumor responses. We previously reported complete remissions (CR) and prolonged persistence in children and adults with relapsed/refractory acute lymphoblastic leukemia (ALL) treated with CD19-specific CAR-modified T cells (CTL019). We now report on outcomes and longer follow-up of 59 children and young adults with relapsed/refractory ALL enrolled on the pediatric phase 1/2a trial of CTL019.
Aims
Determine the safety and efficacy of CTL019 in pediatric patients with relapsed/refractory CD19+ ALL. Determine the safety and efficacy of CTL019 in pediatric patients with a history of CNS involvement of ALL. Assess relapse-free survival (RFS) and overall survival (OS) after CTL019.
Methods
After informed consent, patient-derived T cells were transduced with a lentiviral vector encoding a CAR composed of anti-CD19 scFv, CD3z, and 4-1BB domains, activated/expanded ex vivo with anti-CD3/CD28 beads, and then infused at a dose of 107 to 108 cells/kg with a transduction efficiency of 2.3-45%. 54/59 patients received lymphodepleting chemotherapy the week prior to cell infusion.
Results
Of 59 patients aged 20mo-24y with CD19+ ALL, 44 had detectable disease prior to CTL019 cell infusion, while 15 were minimal residual disease (MRD)-negative. 39 were treated for relapse after prior stem cell transplant (SCT). 15 patients had CNS disease within a year of infusion. At assessment 1 month after infusion, 55/59 (93%) were in CR. MRD <0.01% by flow cytometry was achieved in 52 patients. CTL019 cells were detected in the CSF, all patients achieved CR in the CNS (including 4 patients with CSF blasts detected the day prior to infusion), and no CNS relapses have been seen. With median follow-up 12 mo (1-43 mo), 34 patients had ongoing CR, with only 6 receiving subsequent therapy (5 SCT, 1 donor lymphocyte infusion), RFS was 76% (95% CI, 65-89%) at 6 mo and 55% at 12 mo (95% CI, 42-73%), and OS was 79% (95% CI, 69-91%) at 12 mo. 20 patients subsequently relapsed, 13 with CD19-negative disease. CTL019 persistence was accompanied by B cell aplasia, which continued up to last assessment (1-39 mo) in 24/34 patients with ongoing CR. Cytokine release syndrome (CRS) was seen in 88% of patients. Severe CRS requiring hemodynamic or respiratory support occurred in 27%, was associated with high disease burden, and was reversed with the anti-IL6R agent tocilizumab. We could predict development of severe CRS through regression modeling using IFNγ, sgp130, and IL1RA measured in the first 72h (sensitivity 86%, specificity 89%, AUC 0.93).
Conclusion
Single-agent CTL019 immunotherapy can induce potent responses in patients with relapsed/refractory ALL and can control CNS leukemia. Durable remissions were observed without subsequent SCT. Phase 2 multisite and global registration trials of CTL019 are in progress.
Session topic: Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Adoptive immunotherapy, Antigen-specific T cells, Cellular therapy
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Auditorium 2
Background
Targeted immunotherapy with chimeric antigen receptor (CAR)-modified T cells can produce potent anti-tumor responses. We previously reported complete remissions (CR) and prolonged persistence in children and adults with relapsed/refractory acute lymphoblastic leukemia (ALL) treated with CD19-specific CAR-modified T cells (CTL019). We now report on outcomes and longer follow-up of 59 children and young adults with relapsed/refractory ALL enrolled on the pediatric phase 1/2a trial of CTL019.
Aims
Determine the safety and efficacy of CTL019 in pediatric patients with relapsed/refractory CD19+ ALL. Determine the safety and efficacy of CTL019 in pediatric patients with a history of CNS involvement of ALL. Assess relapse-free survival (RFS) and overall survival (OS) after CTL019.
Methods
After informed consent, patient-derived T cells were transduced with a lentiviral vector encoding a CAR composed of anti-CD19 scFv, CD3z, and 4-1BB domains, activated/expanded ex vivo with anti-CD3/CD28 beads, and then infused at a dose of 107 to 108 cells/kg with a transduction efficiency of 2.3-45%. 54/59 patients received lymphodepleting chemotherapy the week prior to cell infusion.
Results
Of 59 patients aged 20mo-24y with CD19+ ALL, 44 had detectable disease prior to CTL019 cell infusion, while 15 were minimal residual disease (MRD)-negative. 39 were treated for relapse after prior stem cell transplant (SCT). 15 patients had CNS disease within a year of infusion. At assessment 1 month after infusion, 55/59 (93%) were in CR. MRD <0.01% by flow cytometry was achieved in 52 patients. CTL019 cells were detected in the CSF, all patients achieved CR in the CNS (including 4 patients with CSF blasts detected the day prior to infusion), and no CNS relapses have been seen. With median follow-up 12 mo (1-43 mo), 34 patients had ongoing CR, with only 6 receiving subsequent therapy (5 SCT, 1 donor lymphocyte infusion), RFS was 76% (95% CI, 65-89%) at 6 mo and 55% at 12 mo (95% CI, 42-73%), and OS was 79% (95% CI, 69-91%) at 12 mo. 20 patients subsequently relapsed, 13 with CD19-negative disease. CTL019 persistence was accompanied by B cell aplasia, which continued up to last assessment (1-39 mo) in 24/34 patients with ongoing CR. Cytokine release syndrome (CRS) was seen in 88% of patients. Severe CRS requiring hemodynamic or respiratory support occurred in 27%, was associated with high disease burden, and was reversed with the anti-IL6R agent tocilizumab. We could predict development of severe CRS through regression modeling using IFNγ, sgp130, and IL1RA measured in the first 72h (sensitivity 86%, specificity 89%, AUC 0.93).
Conclusion
Single-agent CTL019 immunotherapy can induce potent responses in patients with relapsed/refractory ALL and can control CNS leukemia. Durable remissions were observed without subsequent SCT. Phase 2 multisite and global registration trials of CTL019 are in progress.
Session topic: Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Adoptive immunotherapy, Antigen-specific T cells, Cellular therapy
Abstract: S497
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Auditorium 2
Background
Targeted immunotherapy with chimeric antigen receptor (CAR)-modified T cells can produce potent anti-tumor responses. We previously reported complete remissions (CR) and prolonged persistence in children and adults with relapsed/refractory acute lymphoblastic leukemia (ALL) treated with CD19-specific CAR-modified T cells (CTL019). We now report on outcomes and longer follow-up of 59 children and young adults with relapsed/refractory ALL enrolled on the pediatric phase 1/2a trial of CTL019.
Aims
Determine the safety and efficacy of CTL019 in pediatric patients with relapsed/refractory CD19+ ALL. Determine the safety and efficacy of CTL019 in pediatric patients with a history of CNS involvement of ALL. Assess relapse-free survival (RFS) and overall survival (OS) after CTL019.
Methods
After informed consent, patient-derived T cells were transduced with a lentiviral vector encoding a CAR composed of anti-CD19 scFv, CD3z, and 4-1BB domains, activated/expanded ex vivo with anti-CD3/CD28 beads, and then infused at a dose of 107 to 108 cells/kg with a transduction efficiency of 2.3-45%. 54/59 patients received lymphodepleting chemotherapy the week prior to cell infusion.
Results
Of 59 patients aged 20mo-24y with CD19+ ALL, 44 had detectable disease prior to CTL019 cell infusion, while 15 were minimal residual disease (MRD)-negative. 39 were treated for relapse after prior stem cell transplant (SCT). 15 patients had CNS disease within a year of infusion. At assessment 1 month after infusion, 55/59 (93%) were in CR. MRD <0.01% by flow cytometry was achieved in 52 patients. CTL019 cells were detected in the CSF, all patients achieved CR in the CNS (including 4 patients with CSF blasts detected the day prior to infusion), and no CNS relapses have been seen. With median follow-up 12 mo (1-43 mo), 34 patients had ongoing CR, with only 6 receiving subsequent therapy (5 SCT, 1 donor lymphocyte infusion), RFS was 76% (95% CI, 65-89%) at 6 mo and 55% at 12 mo (95% CI, 42-73%), and OS was 79% (95% CI, 69-91%) at 12 mo. 20 patients subsequently relapsed, 13 with CD19-negative disease. CTL019 persistence was accompanied by B cell aplasia, which continued up to last assessment (1-39 mo) in 24/34 patients with ongoing CR. Cytokine release syndrome (CRS) was seen in 88% of patients. Severe CRS requiring hemodynamic or respiratory support occurred in 27%, was associated with high disease burden, and was reversed with the anti-IL6R agent tocilizumab. We could predict development of severe CRS through regression modeling using IFNγ, sgp130, and IL1RA measured in the first 72h (sensitivity 86%, specificity 89%, AUC 0.93).
Conclusion
Single-agent CTL019 immunotherapy can induce potent responses in patients with relapsed/refractory ALL and can control CNS leukemia. Durable remissions were observed without subsequent SCT. Phase 2 multisite and global registration trials of CTL019 are in progress.
Session topic: Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Adoptive immunotherapy, Antigen-specific T cells, Cellular therapy
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Auditorium 2
Background
Targeted immunotherapy with chimeric antigen receptor (CAR)-modified T cells can produce potent anti-tumor responses. We previously reported complete remissions (CR) and prolonged persistence in children and adults with relapsed/refractory acute lymphoblastic leukemia (ALL) treated with CD19-specific CAR-modified T cells (CTL019). We now report on outcomes and longer follow-up of 59 children and young adults with relapsed/refractory ALL enrolled on the pediatric phase 1/2a trial of CTL019.
Aims
Determine the safety and efficacy of CTL019 in pediatric patients with relapsed/refractory CD19+ ALL. Determine the safety and efficacy of CTL019 in pediatric patients with a history of CNS involvement of ALL. Assess relapse-free survival (RFS) and overall survival (OS) after CTL019.
Methods
After informed consent, patient-derived T cells were transduced with a lentiviral vector encoding a CAR composed of anti-CD19 scFv, CD3z, and 4-1BB domains, activated/expanded ex vivo with anti-CD3/CD28 beads, and then infused at a dose of 107 to 108 cells/kg with a transduction efficiency of 2.3-45%. 54/59 patients received lymphodepleting chemotherapy the week prior to cell infusion.
Results
Of 59 patients aged 20mo-24y with CD19+ ALL, 44 had detectable disease prior to CTL019 cell infusion, while 15 were minimal residual disease (MRD)-negative. 39 were treated for relapse after prior stem cell transplant (SCT). 15 patients had CNS disease within a year of infusion. At assessment 1 month after infusion, 55/59 (93%) were in CR. MRD <0.01% by flow cytometry was achieved in 52 patients. CTL019 cells were detected in the CSF, all patients achieved CR in the CNS (including 4 patients with CSF blasts detected the day prior to infusion), and no CNS relapses have been seen. With median follow-up 12 mo (1-43 mo), 34 patients had ongoing CR, with only 6 receiving subsequent therapy (5 SCT, 1 donor lymphocyte infusion), RFS was 76% (95% CI, 65-89%) at 6 mo and 55% at 12 mo (95% CI, 42-73%), and OS was 79% (95% CI, 69-91%) at 12 mo. 20 patients subsequently relapsed, 13 with CD19-negative disease. CTL019 persistence was accompanied by B cell aplasia, which continued up to last assessment (1-39 mo) in 24/34 patients with ongoing CR. Cytokine release syndrome (CRS) was seen in 88% of patients. Severe CRS requiring hemodynamic or respiratory support occurred in 27%, was associated with high disease burden, and was reversed with the anti-IL6R agent tocilizumab. We could predict development of severe CRS through regression modeling using IFNγ, sgp130, and IL1RA measured in the first 72h (sensitivity 86%, specificity 89%, AUC 0.93).
Conclusion
Single-agent CTL019 immunotherapy can induce potent responses in patients with relapsed/refractory ALL and can control CNS leukemia. Durable remissions were observed without subsequent SCT. Phase 2 multisite and global registration trials of CTL019 are in progress.
Session topic: Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Adoptive immunotherapy, Antigen-specific T cells, Cellular therapy
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