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Lymphoma is a common malignant tumor originating from the lymphoid hematopoietic system, and it is also one of the tumors with a high incidence in recent years
.
The disease control rate and cure rate of lymphoma are relatively high.
After standardized treatment and management of patients, the survival period can be significantly prolonged
.
In order to further discuss the diagnosis, treatment and development of lymphoma in China, a series of activities of the Lymphocytic Disease Group of the Hematology Branch of the Chinese Medical Association-the 2nd Bethune Lymphoma Youth Forum in 2021 will be held online on May 29, 2021
.
At this meeting, Professor Qian Wenbin from the Second Affiliated Hospital of Zhejiang University School of Medicine gave a keynote report on "The Latest Progress in the Research of Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy for B-Cell Lymphoma".
The content is organized as follows
.
Research progress of CAR-T therapy in aggressive lymphoma and indolent lymphoma Professor Qian Wenbin first introduced the research progress of CAR-T therapy in aggressive lymphoma and indolent lymphoma
.
The second-generation CD19 CAR-T therapy has entered the clinical application stage of B-cell lymphoma
.
The currently published real-world research data of CD19 CAR-T therapy are close to clinical research data: ZUMA-1 research and real-world research show that the overall response rate of Axicabtagene Ciloleucel (Axi-cel) in the treatment of large B-cell lymphoma (LBCL) ( ORR) were 82% and 70%; the JULIET study and the real-world study showed that the complete remission (CR) rate of Tisagenlecleucel (Tisa-cel) in the treatment of diffuse large B-cell lymphoma (DLBCL) was 40% and 38%, respectively
.
In addition, CD19 CAR-T has also achieved good efficacy in mantle cell lymphoma (MCL).
The results of the study published in 2020 show that the ORR of Brexucabtagene Autoleucel for MCL treatment reached 93%, and the CR rate reached 67%, 12 months The rate of progression-free survival (PFS) and overall survival (OS) were 61% and 83%, respectively
.
In addition to aggressive lymphoma, the second-generation CD19 CAR-T has also achieved good curative effect in indolent lymphoma, and at the same time demonstrated curative effect that is not inferior to aggressive lymphoma
.
The results of the ZUMA-5 study announced at the EHA meeting in 2020 showed that the ORR of Axi-cel in the treatment of relapsed and refractory indolent non-Hodgkin’s lymphoma (R/R iNHL) reached 93%, and the CR rate reached 80% (follicular lymphoma).
Tumor: 81%, marginal zone lymphoma: 75%)
.
At a median follow-up of 15.
3 months, the patient's median PFS was 23.
5 months, and the median OS did not reach
.
The research progress of CAR-T therapy combined with PD-1/PD-L1 monoclonal antibody is to further improve the efficacy of CD19 CAR-T therapy in patients with lymphoma.
Some studies have explored the combination of CD19 CAR-T therapy with other drugs.
Both have achieved good results.
For example, a study of CD19 CAR-T therapy combined with PD-1 monoclonal antibody in the treatment of relapsed and refractory aggressive lymphomas announced at the ICML meeting in 2019 showed that the combined program was compared with CD19 CAR alone.
-T achieved better curative effect, with a CR rate of 79%
.
At the 2020 EHA meeting, the results of the study of Axi-cel combined with PD-1 monoclonal antibody in the treatment of relapsed and refractory LBCL were announced
.
The combined program has an ORR of 75% and a CR rate of 46% in relapsed and refractory LBCL.
At the same time, the combined program is safe and does not further increase the incidence of cytokine release syndrome (CRS) and neurotoxicity
.
Professor Qian Wenbin said that for LBCL patients with positive PD-L1 expression, this combination scheme is a treatment option that deserves attention
.
Subsequently, Professor Qian Wenbin introduced a domestic study to explore the efficacy of CD19 CAR-T therapy expressing PD-1/CD28 conversion receptors in PD-1 positive LBCL
.
Since the PD-1/CD28 conversion receptor can block the signal pathway of PD-1/PD-L1 immune checkpoints, and at the same time stimulate the activity of CAR-T cells through CD28 signals, the CAR-T therapy has shown a relatively outstanding performance.
Curative effect
.
The results of the Phase Ib study showed that the CR rate of LBCL patients reached 41.
2%
.
At the same time, patients with CR have better long-term survival, with an OS rate of 78% at 15 months
.
Research progress of bispecific CAR-T Professor Qian Wenbin said that in addition to the second-generation CD19 CAR-T therapy and combination therapy, bispecific CAR-T is also a direction worthy of attention at present
.
Related foreign research results show that bispecific CAR-T therapy has stronger specificity for tumor recognition, lower off-target effect, and safety is not inferior to CD19 CAR-T therapy.
The incidence of grade 3-4 CRS is only 5%
.
This advantage has also been confirmed in a number of clinical studies.
Two clinical studies of CD19 combined with CD22 CAR-T in the treatment of DLBCL have shown that bispecific CAR-T therapy is better than CD19 CAR-T therapy in DLBCL patients
.
Research progress on salvage treatment after CAR-T treatment fails.
Although CAR-T treatment has achieved good results in the treatment of B-cell lymphoma, 40%-50% of patients still cannot obtain CR after CAR-T treatment.
Another 10%-20% of patients who reach CR after CAR-T treatment will have disease progression
.
A recently published study explored the efficacy of rescue treatment options such as immune checkpoint inhibitors, chemotherapy, lenalidomide-based treatment options, and radiotherapy in patients who have failed CAR-T treatment
.
The results of the study show that some patients can still obtain CR from other salvage treatments (CR rate, immune checkpoint inhibitor: 18%; lenalidomide-based treatment: 19%, chemotherapy: 12%), but Overall survival is still poor, with a median OS of 331 days for patients treated with immune checkpoint inhibitors, and a median OS of only 104 days for patients receiving chemotherapy
.
Another study used CD19 CAR-T again for patients who failed CD19 CAR-T treatment.
The results of the study showed that the CR rate of NHL patients who received CD19 CAR-T again was 19%.
Compared with other therapies, it did not show an advantage in curative effect.
.
Professor Qian Wenbin said that how to improve the prognosis of these patients with failed CAR-T treatments needs to be explored in more clinical studies in the future
.
Summary Professor Qian Wenbin concluded: CAR-T therapy has achieved good results in B-cell lymphoma, but currently about 50% of patients still cannot benefit from CAR-T therapy, and about 20% of patients Disease progression after obtaining CR
.
The efficacy and safety of other therapies such as target-optimized bispecific CAR-T, humanized CAR-T targeting antigen, CAR-T and immune checkpoint inhibitors and other therapies are worthy of further exploration.
How to improve tumor microbe Environment and reducing T cell exhaustion are also important research directions for CAR-T in the future
.
Professor Qian Wenbin, Chief Physician, Doctoral Supervisor, Director of the Department of Hematology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Deputy Director, Institute of Hematology, Zhejiang University, Deputy Director, Lymphoma Professional Committee, China Association for Geriatric Healthcare, and Hematology Oncology, China Anti-Cancer Association Committee Member, Lymphocytic Disease Group and Infection Group, Chinese Medical Association Hematology Branch Committee Member, CSCO China Anti-Lymphoma Alliance Expert Committee Member, Standing Director, Rare Disease Branch of Chinese Research Hospital Association, Designated Chairman, Hematology Branch of Zhejiang Medical Association, Zhejiang Province The vice president of the Hematology Physician Branch of the Physician Association stamped "read the original text", we will make progress together
.
The disease control rate and cure rate of lymphoma are relatively high.
After standardized treatment and management of patients, the survival period can be significantly prolonged
.
In order to further discuss the diagnosis, treatment and development of lymphoma in China, a series of activities of the Lymphocytic Disease Group of the Hematology Branch of the Chinese Medical Association-the 2nd Bethune Lymphoma Youth Forum in 2021 will be held online on May 29, 2021
.
At this meeting, Professor Qian Wenbin from the Second Affiliated Hospital of Zhejiang University School of Medicine gave a keynote report on "The Latest Progress in the Research of Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy for B-Cell Lymphoma".
The content is organized as follows
.
Research progress of CAR-T therapy in aggressive lymphoma and indolent lymphoma Professor Qian Wenbin first introduced the research progress of CAR-T therapy in aggressive lymphoma and indolent lymphoma
.
The second-generation CD19 CAR-T therapy has entered the clinical application stage of B-cell lymphoma
.
The currently published real-world research data of CD19 CAR-T therapy are close to clinical research data: ZUMA-1 research and real-world research show that the overall response rate of Axicabtagene Ciloleucel (Axi-cel) in the treatment of large B-cell lymphoma (LBCL) ( ORR) were 82% and 70%; the JULIET study and the real-world study showed that the complete remission (CR) rate of Tisagenlecleucel (Tisa-cel) in the treatment of diffuse large B-cell lymphoma (DLBCL) was 40% and 38%, respectively
.
In addition, CD19 CAR-T has also achieved good efficacy in mantle cell lymphoma (MCL).
The results of the study published in 2020 show that the ORR of Brexucabtagene Autoleucel for MCL treatment reached 93%, and the CR rate reached 67%, 12 months The rate of progression-free survival (PFS) and overall survival (OS) were 61% and 83%, respectively
.
In addition to aggressive lymphoma, the second-generation CD19 CAR-T has also achieved good curative effect in indolent lymphoma, and at the same time demonstrated curative effect that is not inferior to aggressive lymphoma
.
The results of the ZUMA-5 study announced at the EHA meeting in 2020 showed that the ORR of Axi-cel in the treatment of relapsed and refractory indolent non-Hodgkin’s lymphoma (R/R iNHL) reached 93%, and the CR rate reached 80% (follicular lymphoma).
Tumor: 81%, marginal zone lymphoma: 75%)
.
At a median follow-up of 15.
3 months, the patient's median PFS was 23.
5 months, and the median OS did not reach
.
The research progress of CAR-T therapy combined with PD-1/PD-L1 monoclonal antibody is to further improve the efficacy of CD19 CAR-T therapy in patients with lymphoma.
Some studies have explored the combination of CD19 CAR-T therapy with other drugs.
Both have achieved good results.
For example, a study of CD19 CAR-T therapy combined with PD-1 monoclonal antibody in the treatment of relapsed and refractory aggressive lymphomas announced at the ICML meeting in 2019 showed that the combined program was compared with CD19 CAR alone.
-T achieved better curative effect, with a CR rate of 79%
.
At the 2020 EHA meeting, the results of the study of Axi-cel combined with PD-1 monoclonal antibody in the treatment of relapsed and refractory LBCL were announced
.
The combined program has an ORR of 75% and a CR rate of 46% in relapsed and refractory LBCL.
At the same time, the combined program is safe and does not further increase the incidence of cytokine release syndrome (CRS) and neurotoxicity
.
Professor Qian Wenbin said that for LBCL patients with positive PD-L1 expression, this combination scheme is a treatment option that deserves attention
.
Subsequently, Professor Qian Wenbin introduced a domestic study to explore the efficacy of CD19 CAR-T therapy expressing PD-1/CD28 conversion receptors in PD-1 positive LBCL
.
Since the PD-1/CD28 conversion receptor can block the signal pathway of PD-1/PD-L1 immune checkpoints, and at the same time stimulate the activity of CAR-T cells through CD28 signals, the CAR-T therapy has shown a relatively outstanding performance.
Curative effect
.
The results of the Phase Ib study showed that the CR rate of LBCL patients reached 41.
2%
.
At the same time, patients with CR have better long-term survival, with an OS rate of 78% at 15 months
.
Research progress of bispecific CAR-T Professor Qian Wenbin said that in addition to the second-generation CD19 CAR-T therapy and combination therapy, bispecific CAR-T is also a direction worthy of attention at present
.
Related foreign research results show that bispecific CAR-T therapy has stronger specificity for tumor recognition, lower off-target effect, and safety is not inferior to CD19 CAR-T therapy.
The incidence of grade 3-4 CRS is only 5%
.
This advantage has also been confirmed in a number of clinical studies.
Two clinical studies of CD19 combined with CD22 CAR-T in the treatment of DLBCL have shown that bispecific CAR-T therapy is better than CD19 CAR-T therapy in DLBCL patients
.
Research progress on salvage treatment after CAR-T treatment fails.
Although CAR-T treatment has achieved good results in the treatment of B-cell lymphoma, 40%-50% of patients still cannot obtain CR after CAR-T treatment.
Another 10%-20% of patients who reach CR after CAR-T treatment will have disease progression
.
A recently published study explored the efficacy of rescue treatment options such as immune checkpoint inhibitors, chemotherapy, lenalidomide-based treatment options, and radiotherapy in patients who have failed CAR-T treatment
.
The results of the study show that some patients can still obtain CR from other salvage treatments (CR rate, immune checkpoint inhibitor: 18%; lenalidomide-based treatment: 19%, chemotherapy: 12%), but Overall survival is still poor, with a median OS of 331 days for patients treated with immune checkpoint inhibitors, and a median OS of only 104 days for patients receiving chemotherapy
.
Another study used CD19 CAR-T again for patients who failed CD19 CAR-T treatment.
The results of the study showed that the CR rate of NHL patients who received CD19 CAR-T again was 19%.
Compared with other therapies, it did not show an advantage in curative effect.
.
Professor Qian Wenbin said that how to improve the prognosis of these patients with failed CAR-T treatments needs to be explored in more clinical studies in the future
.
Summary Professor Qian Wenbin concluded: CAR-T therapy has achieved good results in B-cell lymphoma, but currently about 50% of patients still cannot benefit from CAR-T therapy, and about 20% of patients Disease progression after obtaining CR
.
The efficacy and safety of other therapies such as target-optimized bispecific CAR-T, humanized CAR-T targeting antigen, CAR-T and immune checkpoint inhibitors and other therapies are worthy of further exploration.
How to improve tumor microbe Environment and reducing T cell exhaustion are also important research directions for CAR-T in the future
.
Professor Qian Wenbin, Chief Physician, Doctoral Supervisor, Director of the Department of Hematology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Deputy Director, Institute of Hematology, Zhejiang University, Deputy Director, Lymphoma Professional Committee, China Association for Geriatric Healthcare, and Hematology Oncology, China Anti-Cancer Association Committee Member, Lymphocytic Disease Group and Infection Group, Chinese Medical Association Hematology Branch Committee Member, CSCO China Anti-Lymphoma Alliance Expert Committee Member, Standing Director, Rare Disease Branch of Chinese Research Hospital Association, Designated Chairman, Hematology Branch of Zhejiang Medical Association, Zhejiang Province The vice president of the Hematology Physician Branch of the Physician Association stamped "read the original text", we will make progress together
