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In recent years, the clinical application of new drugs including proteasome inhibitors (PIs), immunomodulators (IMiDs) and monoclonal antibodies has significantly improved the survival of patients with multiple myeloma (MM), but the disease is still incurable.
All patients will face relapse and refractory treatment
.
Chimeric Antigen Receptor (CAR) T cell therapy has opened a new chapter in MM treatment.
Past research results have shown that CAR-T cell therapy targeting BCMA has an overall response rate (ORR) in patients with relapsed and refractory MM (RRMM).
) Is 33%-88%, but BCMA CAR-T cell therapy treatment of RRMM patients to achieve durable remission is still a huge challenge.
During the median follow-up time of 2-15 months, 28%-88% of patients have Relapse or disease progression
.
The proliferation level of CAR-T cells and the duration of their existence in the blood may be one of the decisive factors for the duration of treatment response (DOR)
.
Previous studies have shown that CARs with humanized or fully humanized antibody single-chain variable region fragments (scFvs) may be expected to bypass potential host anti-CAR immunogenicity and retain anti-tumor activity
.
Recently, the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, conducted a phase I clinical study of a new fully humanized BCMA CAR-T cell (CT103A) to evaluate the safety and efficacy of CT103A in RRMM patients
.
Research method The study included RRMM patients ≥18 years old and ≤70 years old.
All eligible patients underwent peripheral blood mononuclear cell (PBMC) collection through leukocyte separation and received 3 consecutive CT103A infusions.
FC regimen (fludarabine 25 mg/m2/d and cyclophosphamide 20 mg/kg/d) on day (-4 to -2) lymphocyte depletion chemotherapy
.
CT103A is infused in a "3+3" dose-escalation mode, with 1×106, 3×106, and 6×106 CAR-T cells/kg in the dose-escalation phase, and 1×106 CAR-T in the expansion cohort Cells/kg infusion
.
The primary study endpoint is to evaluate safety and tolerability, including dose-limiting toxicity (DLT) and maximum tolerated dose, and determine the recommended phase II dose of CT103A
.
The secondary study endpoints are the efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of CT103A
.
Study Results 1 Patient characteristics The study screened a total of 24 patients, and 18 patients were ultimately treated with CT103A, with a median age of 53.
5 years (range: 38-66 years)
.
Patients with high-risk cytogenetics accounted for 38.
9%, patients with extramedullary lesions (EMM) accounted for 27.
8%, the median number of previous treatments was 4, and 4 patients had previously received murine BCMA CAR-T cell therapy
.
2 Overall, the patient’s ORR was 100%, and 72.
2% of the patients achieved complete remission (CR) or strict complete remission (sCR)
.
Among the 5 EMM patients, 4 patients with multiple extramedullary lesions developed disease progression (PD) or recurrence
.
Among the 4 patients who had previously received mouse-derived BCMA CAR-T cell therapy, 3 cases achieved CR and 1 case achieved partial remission (PR)
.
By the cut-off date, neither the median progression-free survival (PFS) nor the overall survival (OS) were reached; the 1-year PFS rate and OS rate were 58.
3% and 75%, respectively; the 1-year PFS rate for patients without EMM was 79.
1 %
.
3 Safety The most common adverse event (AE) of patients in this study was hematological toxicity.
70.
6% of patients had grade 1 or 2 cytokine release syndrome (CRS); no immune effector cell-related neurotoxicity synthesis was observed Levy (ICANS)
.
4 After the infusion of CAR-T cell dynamics until the end of the test, CAR-T cells can still be detected in 77.
8% of patients; the median duration of CAR-T cells in patients is 307.
5 days
.
On the 30th day after CT103A infusion, higher levels of CT103A cells can be detected in the peripheral blood of patients who have previously received murine BCMA CAR-T cell therapy
.
Research conclusions The results of this phase I clinical study show that CT103A has an ORR of 100% in RRMM patients, and patients who have relapsed after previous treatment with mouse-derived BCMA CAR-T cells may still benefit from CT103A treatment
.
References: Di Wang, Jue Wang, Guang Hu, et al.
A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma.
Blood.
2021 May 27;137(21) :2890-2901.
Poke "read the original", we will make progress together
All patients will face relapse and refractory treatment
.
Chimeric Antigen Receptor (CAR) T cell therapy has opened a new chapter in MM treatment.
Past research results have shown that CAR-T cell therapy targeting BCMA has an overall response rate (ORR) in patients with relapsed and refractory MM (RRMM).
) Is 33%-88%, but BCMA CAR-T cell therapy treatment of RRMM patients to achieve durable remission is still a huge challenge.
During the median follow-up time of 2-15 months, 28%-88% of patients have Relapse or disease progression
.
The proliferation level of CAR-T cells and the duration of their existence in the blood may be one of the decisive factors for the duration of treatment response (DOR)
.
Previous studies have shown that CARs with humanized or fully humanized antibody single-chain variable region fragments (scFvs) may be expected to bypass potential host anti-CAR immunogenicity and retain anti-tumor activity
.
Recently, the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, conducted a phase I clinical study of a new fully humanized BCMA CAR-T cell (CT103A) to evaluate the safety and efficacy of CT103A in RRMM patients
.
Research method The study included RRMM patients ≥18 years old and ≤70 years old.
All eligible patients underwent peripheral blood mononuclear cell (PBMC) collection through leukocyte separation and received 3 consecutive CT103A infusions.
FC regimen (fludarabine 25 mg/m2/d and cyclophosphamide 20 mg/kg/d) on day (-4 to -2) lymphocyte depletion chemotherapy
.
CT103A is infused in a "3+3" dose-escalation mode, with 1×106, 3×106, and 6×106 CAR-T cells/kg in the dose-escalation phase, and 1×106 CAR-T in the expansion cohort Cells/kg infusion
.
The primary study endpoint is to evaluate safety and tolerability, including dose-limiting toxicity (DLT) and maximum tolerated dose, and determine the recommended phase II dose of CT103A
.
The secondary study endpoints are the efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of CT103A
.
Study Results 1 Patient characteristics The study screened a total of 24 patients, and 18 patients were ultimately treated with CT103A, with a median age of 53.
5 years (range: 38-66 years)
.
Patients with high-risk cytogenetics accounted for 38.
9%, patients with extramedullary lesions (EMM) accounted for 27.
8%, the median number of previous treatments was 4, and 4 patients had previously received murine BCMA CAR-T cell therapy
.
2 Overall, the patient’s ORR was 100%, and 72.
2% of the patients achieved complete remission (CR) or strict complete remission (sCR)
.
Among the 5 EMM patients, 4 patients with multiple extramedullary lesions developed disease progression (PD) or recurrence
.
Among the 4 patients who had previously received mouse-derived BCMA CAR-T cell therapy, 3 cases achieved CR and 1 case achieved partial remission (PR)
.
By the cut-off date, neither the median progression-free survival (PFS) nor the overall survival (OS) were reached; the 1-year PFS rate and OS rate were 58.
3% and 75%, respectively; the 1-year PFS rate for patients without EMM was 79.
1 %
.
3 Safety The most common adverse event (AE) of patients in this study was hematological toxicity.
70.
6% of patients had grade 1 or 2 cytokine release syndrome (CRS); no immune effector cell-related neurotoxicity synthesis was observed Levy (ICANS)
.
4 After the infusion of CAR-T cell dynamics until the end of the test, CAR-T cells can still be detected in 77.
8% of patients; the median duration of CAR-T cells in patients is 307.
5 days
.
On the 30th day after CT103A infusion, higher levels of CT103A cells can be detected in the peripheral blood of patients who have previously received murine BCMA CAR-T cell therapy
.
Research conclusions The results of this phase I clinical study show that CT103A has an ORR of 100% in RRMM patients, and patients who have relapsed after previous treatment with mouse-derived BCMA CAR-T cells may still benefit from CT103A treatment
.
References: Di Wang, Jue Wang, Guang Hu, et al.
A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma.
Blood.
2021 May 27;137(21) :2890-2901.
Poke "read the original", we will make progress together
