Contributions
Abstract: S827
Type: Oral Presentation
Presentation during EHA24: On Saturday, June 15, 2019 from 12:30 - 12:45
Location: Auditorium
Background
Previous studies indicate patients with relapsed/refractory multiple myeloma (RRMM) who receive high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells is not effective. To solve this dilemma, we have developed a novel BCMA-targeting CAR-T (CT103A) with a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3z activation domains.
Aims
The primary objectives are to characterize the safety and tolerability in patients with R/R MM. The secondary objectives include evaluation of anti-myeloma activity, cytokines, CAR-T cell persistence, and pharmacokinetics.
Methods
ChiCTR1800018137 is a single-center and single-arm trial of CT103A in patients with RRMM. Between September 21, 2018, and January 21, 2019, nine patients (including 3 patients having relapsed after being given a murine BCMA CAR-T) received CT103A in 3+3 dose-escalation trial (three doses at 1, 3, 6 ×106/kg) after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. All Patients had received a median of 4 prior lines (range 3 - 5) of MM therapy.
Results
At the time of the February 4, 2019 data analysis, the overall response rate was 100% (Table1), and all patients had a rapid response within 14 days, with 67% (2/3) reaching CR/sCR at the lowest dose. The pharmacokinetics of CT103A were assessed by a digital polymerase chain reaction. Robust expansions were seen even at the lowest dosage level. In addition, Cmax and AUC0-28 reached levels comparable to reported CD19 CAR-T. In the first two dose groups, the grade of cytokine release syndrome (CRS) was 0 - 2. In the 6 ×106 /kg dose group, DLT had been observed in one patient.
Table 1. Treatment Response (Case 1,5 and 7 are murine BCMA CAR-T relapse patients)
| Case | CAR T-Cell Dose (×106/kg) | D14 | D30 | D60 | D90 | D120 |
| 1 | 1 | CR | CR | CR | CR | CR |
| 2 | 1 | SD | MR | PR | PR | PR |
| 3 | 1 | CR | CR | CR | CR | |
| 4 | 3 | MR | PR | PR | ||
| 5 | 3 | CR | CR | CR | ||
| 6 | 3 | CR | CR | |||
| 7 | 6 | PR | VGPR | |||
| 8 | 6 | PR | ||||
| 9 | 6 | PR |
Conclusion
Data from this early-stage clinical study showed the unparalleled safety and efficacy of CT103A. Major AEs were transient, manageable, and reversible. three patients who relapsed the murine BCMA CAR-T were treated with CT103A, two patients achieved CR, and one patient achieved VGPR. 100% ORR and a rapid response within 2 weeks, suggests CT103A could be developed as a competitive therapeutic to treat patients with RRMM.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Cancer immunotherapy, Myeloma, Treatment
Abstract: S827
Type: Oral Presentation
Presentation during EHA24: On Saturday, June 15, 2019 from 12:30 - 12:45
Location: Auditorium
Background
Previous studies indicate patients with relapsed/refractory multiple myeloma (RRMM) who receive high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells is not effective. To solve this dilemma, we have developed a novel BCMA-targeting CAR-T (CT103A) with a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3z activation domains.
Aims
The primary objectives are to characterize the safety and tolerability in patients with R/R MM. The secondary objectives include evaluation of anti-myeloma activity, cytokines, CAR-T cell persistence, and pharmacokinetics.
Methods
ChiCTR1800018137 is a single-center and single-arm trial of CT103A in patients with RRMM. Between September 21, 2018, and January 21, 2019, nine patients (including 3 patients having relapsed after being given a murine BCMA CAR-T) received CT103A in 3+3 dose-escalation trial (three doses at 1, 3, 6 ×106/kg) after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. All Patients had received a median of 4 prior lines (range 3 - 5) of MM therapy.
Results
At the time of the February 4, 2019 data analysis, the overall response rate was 100% (Table1), and all patients had a rapid response within 14 days, with 67% (2/3) reaching CR/sCR at the lowest dose. The pharmacokinetics of CT103A were assessed by a digital polymerase chain reaction. Robust expansions were seen even at the lowest dosage level. In addition, Cmax and AUC0-28 reached levels comparable to reported CD19 CAR-T. In the first two dose groups, the grade of cytokine release syndrome (CRS) was 0 - 2. In the 6 ×106 /kg dose group, DLT had been observed in one patient.
Table 1. Treatment Response (Case 1,5 and 7 are murine BCMA CAR-T relapse patients)
| Case | CAR T-Cell Dose (×106/kg) | D14 | D30 | D60 | D90 | D120 |
| 1 | 1 | CR | CR | CR | CR | CR |
| 2 | 1 | SD | MR | PR | PR | PR |
| 3 | 1 | CR | CR | CR | CR | |
| 4 | 3 | MR | PR | PR | ||
| 5 | 3 | CR | CR | CR | ||
| 6 | 3 | CR | CR | |||
| 7 | 6 | PR | VGPR | |||
| 8 | 6 | PR | ||||
| 9 | 6 | PR |
Conclusion
Data from this early-stage clinical study showed the unparalleled safety and efficacy of CT103A. Major AEs were transient, manageable, and reversible. three patients who relapsed the murine BCMA CAR-T were treated with CT103A, two patients achieved CR, and one patient achieved VGPR. 100% ORR and a rapid response within 2 weeks, suggests CT103A could be developed as a competitive therapeutic to treat patients with RRMM.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Cancer immunotherapy, Myeloma, Treatment
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