THE HIGHLY CLINICAL EFFICACY AND SAFETY OF THE AUTOLOGOUS ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T CELLS IMMUNOTHERAPY FOR 26 CASES WITH HEAVILY TREATED REFRACTORY B ACUTE LYMPHOBLASTIC LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Pan J. 06/11/16; 135268; S512
Mrs. Jing Pan
Contributions
Contributions
Abstract
Abstract: S512
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Hall C14
Background
the patients with refractory B-ALL are almost incurable by chemotherapy or allo-HSCT. Many data has demonstrated that anti-19-CART cell immunotherapy can result in CR and bridge to allo-HSCT for these patients.
Aims
to evaluate the clinical efficacy and safety of the second generation of anti-CD19-CART cells immunotherapy.
Methods
leukapheresis products from the patients themselves were cultured in the serum free medium containing antibodies to CD3, CD28, and IL2, IL7, IL15, IL21, transduced with the lentivirus encoding anti-CD19-CD3ξ-4-1BB CAR(Figure 1) for 7 days. After leukapheresis, patients received chemotherapy containing fludarabine 30mg/ m2 per day IV and cyclophosphamide 250mg/ m2 per day IV for 3 days except one patient who had persistent cytopenia. On day 7 or/and day 8, the cultured CART cells were infused. Between Jun.31 2015 to Feb. 20 2016, total 26 cases with chemotherapy refractory B-ALL were treated with CART. After infusion of CART, the patients were followed until die, or relapse, or at least 15 days. In the included cases, the median age was 9 years old (2-59 years old), the median observation period was 100 days (19-204 days), and the median prior chemotherapy period was 14 months (1-36 months). 19/26 cases were hematological relapse, with 10/19 complicated extramedullary relapse, 7/26 cases remained minimal residual disease detected by flowcytometry (FCM-MRD) over 3 months although by alternative chemotherapy. Before CART therapy, all patients relapsed during chemotherapy or hadn’t responded to 1 or more cycles of chemotherapy after relapsed except one patient suffered from severe infective pneumonia because she carried inherited immune related gene deficiency (LYST c.6031A＞G/p.I2011V gene mutation) and was intolerated to chemotherapy. Before CART therapy, the median percentage of blasts in BM was 67%(11.5-96%) in the cases with hematological relapse, the FCM-MRD were 0.01%—1.53% in the MRD+ group. The median infused total CD19- CAR T cells was 10 x 104 / kg (0.5-140 x 104 / kg), the median cells transfection efficiency is 19% (1.2- 53.6%), the median cells viability is 85% (43-99.4%).
Results
On day 16 after CART infusion, 15/19 hematological relapse cases achieved CR or CRi (83.3%), 14/15 cases achieved CMR (FCM-MRD negative). 6/7(85.71%) FCM-MRD positive cases achieved CMR (FCM-MRD negative). During the first month, 1 case died from CRS, 2 cases died from leukemia progression. 2/16 who have achieved CR and been follow up for ≥ 60 days relapsed again, 1 is CD19- relapse. 6/6 cases who have achieved CR and bridged to allo-HSCT remain CCMR to now with median follow up period 40 days (24-106 days) after allo-HSCT. The median appearance of CRS was at day 6 (day 1-11), the median CRS grade was 1 (0-5). All MRD+ patients before CART therapy only developed ≤1 grade of CRS. The IL6 and INFγ elevates in PB and CSF in all detected patients (n=4).
Conclusion
Our anti-CD19-CAR T cells immunotherapy can result in high CR/CRi /CMR rate (including extramedullary leukemia) and low TRM for the heavily treated refractory B-ALL, which provide an opportunity to cure these advanced patients by allo-HSCT. The infused CART number in our patients is lower than many reports, which can dramatically reduce the cost of the therapy. The major complication is CRS. CRS grade is associated with the number of malignant B cells in PB. CD19-relapse has been observed.
Session topic: Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Immunotherapy, Relapsed acute lymphoblastic leukemia
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Hall C14
Background
the patients with refractory B-ALL are almost incurable by chemotherapy or allo-HSCT. Many data has demonstrated that anti-19-CART cell immunotherapy can result in CR and bridge to allo-HSCT for these patients.
Aims
to evaluate the clinical efficacy and safety of the second generation of anti-CD19-CART cells immunotherapy.
Methods
leukapheresis products from the patients themselves were cultured in the serum free medium containing antibodies to CD3, CD28, and IL2, IL7, IL15, IL21, transduced with the lentivirus encoding anti-CD19-CD3ξ-4-1BB CAR(Figure 1) for 7 days. After leukapheresis, patients received chemotherapy containing fludarabine 30mg/ m2 per day IV and cyclophosphamide 250mg/ m2 per day IV for 3 days except one patient who had persistent cytopenia. On day 7 or/and day 8, the cultured CART cells were infused. Between Jun.31 2015 to Feb. 20 2016, total 26 cases with chemotherapy refractory B-ALL were treated with CART. After infusion of CART, the patients were followed until die, or relapse, or at least 15 days. In the included cases, the median age was 9 years old (2-59 years old), the median observation period was 100 days (19-204 days), and the median prior chemotherapy period was 14 months (1-36 months). 19/26 cases were hematological relapse, with 10/19 complicated extramedullary relapse, 7/26 cases remained minimal residual disease detected by flowcytometry (FCM-MRD) over 3 months although by alternative chemotherapy. Before CART therapy, all patients relapsed during chemotherapy or hadn’t responded to 1 or more cycles of chemotherapy after relapsed except one patient suffered from severe infective pneumonia because she carried inherited immune related gene deficiency (LYST c.6031A＞G/p.I2011V gene mutation) and was intolerated to chemotherapy. Before CART therapy, the median percentage of blasts in BM was 67%(11.5-96%) in the cases with hematological relapse, the FCM-MRD were 0.01%—1.53% in the MRD+ group. The median infused total CD19- CAR T cells was 10 x 104 / kg (0.5-140 x 104 / kg), the median cells transfection efficiency is 19% (1.2- 53.6%), the median cells viability is 85% (43-99.4%).
Results
On day 16 after CART infusion, 15/19 hematological relapse cases achieved CR or CRi (83.3%), 14/15 cases achieved CMR (FCM-MRD negative). 6/7(85.71%) FCM-MRD positive cases achieved CMR (FCM-MRD negative). During the first month, 1 case died from CRS, 2 cases died from leukemia progression. 2/16 who have achieved CR and been follow up for ≥ 60 days relapsed again, 1 is CD19- relapse. 6/6 cases who have achieved CR and bridged to allo-HSCT remain CCMR to now with median follow up period 40 days (24-106 days) after allo-HSCT. The median appearance of CRS was at day 6 (day 1-11), the median CRS grade was 1 (0-5). All MRD+ patients before CART therapy only developed ≤1 grade of CRS. The IL6 and INFγ elevates in PB and CSF in all detected patients (n=4).
Conclusion
Our anti-CD19-CAR T cells immunotherapy can result in high CR/CRi /CMR rate (including extramedullary leukemia) and low TRM for the heavily treated refractory B-ALL, which provide an opportunity to cure these advanced patients by allo-HSCT. The infused CART number in our patients is lower than many reports, which can dramatically reduce the cost of the therapy. The major complication is CRS. CRS grade is associated with the number of malignant B cells in PB. CD19-relapse has been observed.
Session topic: Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Immunotherapy, Relapsed acute lymphoblastic leukemia
Abstract: S512
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Hall C14
Background
the patients with refractory B-ALL are almost incurable by chemotherapy or allo-HSCT. Many data has demonstrated that anti-19-CART cell immunotherapy can result in CR and bridge to allo-HSCT for these patients.
Aims
to evaluate the clinical efficacy and safety of the second generation of anti-CD19-CART cells immunotherapy.
Methods
leukapheresis products from the patients themselves were cultured in the serum free medium containing antibodies to CD3, CD28, and IL2, IL7, IL15, IL21, transduced with the lentivirus encoding anti-CD19-CD3ξ-4-1BB CAR(Figure 1) for 7 days. After leukapheresis, patients received chemotherapy containing fludarabine 30mg/ m2 per day IV and cyclophosphamide 250mg/ m2 per day IV for 3 days except one patient who had persistent cytopenia. On day 7 or/and day 8, the cultured CART cells were infused. Between Jun.31 2015 to Feb. 20 2016, total 26 cases with chemotherapy refractory B-ALL were treated with CART. After infusion of CART, the patients were followed until die, or relapse, or at least 15 days. In the included cases, the median age was 9 years old (2-59 years old), the median observation period was 100 days (19-204 days), and the median prior chemotherapy period was 14 months (1-36 months). 19/26 cases were hematological relapse, with 10/19 complicated extramedullary relapse, 7/26 cases remained minimal residual disease detected by flowcytometry (FCM-MRD) over 3 months although by alternative chemotherapy. Before CART therapy, all patients relapsed during chemotherapy or hadn’t responded to 1 or more cycles of chemotherapy after relapsed except one patient suffered from severe infective pneumonia because she carried inherited immune related gene deficiency (LYST c.6031A＞G/p.I2011V gene mutation) and was intolerated to chemotherapy. Before CART therapy, the median percentage of blasts in BM was 67%(11.5-96%) in the cases with hematological relapse, the FCM-MRD were 0.01%—1.53% in the MRD+ group. The median infused total CD19- CAR T cells was 10 x 104 / kg (0.5-140 x 104 / kg), the median cells transfection efficiency is 19% (1.2- 53.6%), the median cells viability is 85% (43-99.4%).
Results
On day 16 after CART infusion, 15/19 hematological relapse cases achieved CR or CRi (83.3%), 14/15 cases achieved CMR (FCM-MRD negative). 6/7(85.71%) FCM-MRD positive cases achieved CMR (FCM-MRD negative). During the first month, 1 case died from CRS, 2 cases died from leukemia progression. 2/16 who have achieved CR and been follow up for ≥ 60 days relapsed again, 1 is CD19- relapse. 6/6 cases who have achieved CR and bridged to allo-HSCT remain CCMR to now with median follow up period 40 days (24-106 days) after allo-HSCT. The median appearance of CRS was at day 6 (day 1-11), the median CRS grade was 1 (0-5). All MRD+ patients before CART therapy only developed ≤1 grade of CRS. The IL6 and INFγ elevates in PB and CSF in all detected patients (n=4).
Conclusion
Our anti-CD19-CAR T cells immunotherapy can result in high CR/CRi /CMR rate (including extramedullary leukemia) and low TRM for the heavily treated refractory B-ALL, which provide an opportunity to cure these advanced patients by allo-HSCT. The infused CART number in our patients is lower than many reports, which can dramatically reduce the cost of the therapy. The major complication is CRS. CRS grade is associated with the number of malignant B cells in PB. CD19-relapse has been observed.
Session topic: Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Immunotherapy, Relapsed acute lymphoblastic leukemia
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Hall C14
Background
the patients with refractory B-ALL are almost incurable by chemotherapy or allo-HSCT. Many data has demonstrated that anti-19-CART cell immunotherapy can result in CR and bridge to allo-HSCT for these patients.
Aims
to evaluate the clinical efficacy and safety of the second generation of anti-CD19-CART cells immunotherapy.
Methods
leukapheresis products from the patients themselves were cultured in the serum free medium containing antibodies to CD3, CD28, and IL2, IL7, IL15, IL21, transduced with the lentivirus encoding anti-CD19-CD3ξ-4-1BB CAR(Figure 1) for 7 days. After leukapheresis, patients received chemotherapy containing fludarabine 30mg/ m2 per day IV and cyclophosphamide 250mg/ m2 per day IV for 3 days except one patient who had persistent cytopenia. On day 7 or/and day 8, the cultured CART cells were infused. Between Jun.31 2015 to Feb. 20 2016, total 26 cases with chemotherapy refractory B-ALL were treated with CART. After infusion of CART, the patients were followed until die, or relapse, or at least 15 days. In the included cases, the median age was 9 years old (2-59 years old), the median observation period was 100 days (19-204 days), and the median prior chemotherapy period was 14 months (1-36 months). 19/26 cases were hematological relapse, with 10/19 complicated extramedullary relapse, 7/26 cases remained minimal residual disease detected by flowcytometry (FCM-MRD) over 3 months although by alternative chemotherapy. Before CART therapy, all patients relapsed during chemotherapy or hadn’t responded to 1 or more cycles of chemotherapy after relapsed except one patient suffered from severe infective pneumonia because she carried inherited immune related gene deficiency (LYST c.6031A＞G/p.I2011V gene mutation) and was intolerated to chemotherapy. Before CART therapy, the median percentage of blasts in BM was 67%(11.5-96%) in the cases with hematological relapse, the FCM-MRD were 0.01%—1.53% in the MRD+ group. The median infused total CD19- CAR T cells was 10 x 104 / kg (0.5-140 x 104 / kg), the median cells transfection efficiency is 19% (1.2- 53.6%), the median cells viability is 85% (43-99.4%).
Results
On day 16 after CART infusion, 15/19 hematological relapse cases achieved CR or CRi (83.3%), 14/15 cases achieved CMR (FCM-MRD negative). 6/7(85.71%) FCM-MRD positive cases achieved CMR (FCM-MRD negative). During the first month, 1 case died from CRS, 2 cases died from leukemia progression. 2/16 who have achieved CR and been follow up for ≥ 60 days relapsed again, 1 is CD19- relapse. 6/6 cases who have achieved CR and bridged to allo-HSCT remain CCMR to now with median follow up period 40 days (24-106 days) after allo-HSCT. The median appearance of CRS was at day 6 (day 1-11), the median CRS grade was 1 (0-5). All MRD+ patients before CART therapy only developed ≤1 grade of CRS. The IL6 and INFγ elevates in PB and CSF in all detected patients (n=4).
Conclusion
Our anti-CD19-CAR T cells immunotherapy can result in high CR/CRi /CMR rate (including extramedullary leukemia) and low TRM for the heavily treated refractory B-ALL, which provide an opportunity to cure these advanced patients by allo-HSCT. The infused CART number in our patients is lower than many reports, which can dramatically reduce the cost of the therapy. The major complication is CRS. CRS grade is associated with the number of malignant B cells in PB. CD19-relapse has been observed.
Session topic: Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Immunotherapy, Relapsed acute lymphoblastic leukemia
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