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In recent years, chimeric antigen receptor T cell (CAR-T) therapy has achieved breakthrough results in the field of hematological tumors, and CAR-T-related new drugs have also been launched in China, but there are still many problems that urgently need to be further improved in clinical research, such as Persistence, the influencing factors of curative effect and how to choose effective targets and other issues
.
Recently, the world's premier scientific exchange event in the field of hematology-the American Society of Hematology (ASH) annual meeting is about to be held, and many clinical research results of Lu Daopei Hospital focusing on key issues of CAR-T therapy have once again appeared at the ASH annual meeting
.
On the occasion of the ASH meeting, Yimaitong was fortunate to invite Professor Zhang Xian from the Department of Hematology of Lu Daopei Hospital to share her outstanding research results in the field of CAR-T treatment, which are summarized as follows
.
Yimaitong: Many literatures show that TP53 mutation is a bad prognostic factor for CAR-T products in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).
Can you analyze this? Professor Zhang Xian now has a lot of CAR-T products targeting CD19, and the curative effect is also very good
.
There are more than 1,000 patients with relapsed/refractory B-ALL who received CD19 CAR-T therapy in the single center of Lu Daopei Hospital alone.
We have accumulated a lot of treatment experience
.
In the past two years, two summary analyses of CART treatment in 110 and 254 patients with relapsed/refractory B-ALL in our hospital showed that although the CD19 CAR-T complete remission rate was as high as 90%
.
However, the complete remission rate and long-term survival rate of patients with TP53 mutation and chromosome 17p deletion are lower than those without TP53 mutation and chromosome 17 abnormality.
Whether it is univariate analysis or multivariate analysis, it is confirmed to be independent Poor prognostic factors
.
Further analysis found that even in patients with TP53 mutation and chromosome 17p deletion, the complete remission rate after CD19 CART is as high as 78%, and long-term survival can reach more than 30%
.
In order to further analyze the factors affecting the efficacy of CD19 CAR-T in the TP53 mutation patient group, we screened 64 cases of TP53 mutation and/or from more than 400 patients with relapsed/refractory B-ALL who received CD19 CAR-T therapy.
In patients with chromosome 17p deletion, we analyzed nearly 20 factors that may affect TP53 gene abnormalities that have been reported in the literature.
Finally, it was found that other complex chromosomal abnormalities combined with CAR-T therapy did not bridge allogeneic hematopoietic stem cell transplantation (allo-HSCT).
) Is a very clear independent poor prognostic factor
.
Some other factors can also see the trend of impact on the prognosis, but no statistical difference has been observed in the current sample of 64 cases, and it needs to be observed and counted after further increasing the number of cases
.
Yimaitong: In the treatment of acute leukemia, what is the difference between CD7 CAR-T and CD19 CAR-T? Professor Zhang Xian our hospital started clinical trials of CD7 CAR-T cell therapy in October last year
.
The enrollment was mainly T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) patients, as well as some mature T-cell lymphoma patients
.
Because this patient population is relatively smaller than B-ALL and B-cell lymphoma patients, so far, there are about 70 patients receiving CD7 CAR-T therapy in our hospital
.
Our analysis found that the clinical characteristics of CD7 CAR-T after infusion are very different from those of CD19 CAR-T
.
The heat peak appears earlier after CD7 CAR-T reinfusion, and it is a double heat peak phenomenon
.
Fever will appear in the first 3 days after CD7 CAR-T cell reinfusion, and after a period of calm, there will be a fever peak in 10-21 days
.
The fever peak of CD19 CAR-T is basically in the 7-14 days after CAR-T infusion
.
Therefore, compared with patients who received CD19 CAR-T cells, patients who received CD7 CAR-T cells need to pay more attention to the side effects of CART
.
Except for the different characteristics of fever, there is no significant difference in the incidence of cytokine release syndrome (CRS) and CART-related neurotoxicity after CD7 CAR-T reinfusion compared with the incidence after CD19 CART treatment
.
Yimaitong: Can patients with CD7-positive acute mixed cell leukemia benefit from CD7 CAR-T treatment? How safe is it? Professor Zhang Xian Acute mixed cell leukemia is a rare subtype of acute leukemia that expresses multi-lineage differentiation antigens.
The prognosis is generally poor.
Relapsed/refractory acute mixed cell leukemia has a worse effect of chemotherapy.
Allogeneic hematopoietic stem cell transplantation The prognosis is not ideal, and there is a lack of very effective treatments before CAR-T
.
Based on the above background, we carried out the first clinical study on the treatment of relapsed/refractory acute mixed cell leukemia with CD7 CAR-T therapy
.
It is clear that patients with CD7-positive acute mixed cell leukemia, and even patients who relapse after transplantation, can benefit from CD7 CAR-T therapy, and the safety is within controllable range
.
Although the number of cases is small, it brings hope of cure for this type of patients
.
Yimaitong: You have announced many cutting-edge results at international conferences in the past few years.
What supports you to achieve so many results? Professor Zhang Xian finds suitable treatment options for various relapsed and refractory patients to save one life after another.
This is what our doctors have been doing
.
We have produced many results recently because our Lu Daopei Hospital is a very good medical transformation platform
.
First of all, our hospital has always been patient-centered, and we are very willing to apply cutting-edge medical results and leading treatment methods to patients.
We are willing to seek various new and promising scientific research results to be quickly applied to the clinic, and to strive for new drugs for patients , Immunotherapy products
.
Secondly, we have rich experience in the treatment and management of blood diseases, which can guarantee the safety of patients to the greatest extent
.
Finally, we need to summarize these results and analyze the statistically significant results for academic summary
.
While our hospital continues to explore and innovate in the field of blood diseases, it has been constantly summing up, hoping to bring hope to more patients with blood diseases by sharing our experience
.
Conclusion The annual ASH annual meeting is the top academic conference in the field of global hematology
.
Lu Daopei Hospital has been shortlisted for the ASH annual meeting for consecutive years, fully demonstrating its academic achievements in the industry and also reflecting the recognition of Lu Daopei's medical team by global hematology authorities.
Its excellent test results have been widely praised by the international hematology community
.
It is hoped that this "Chinese power" will continue to explore and lead China's CAR-T therapy to the top of the world's academic world and benefit more patients with blood diseases
.
Professor Zhang Xian, Director of the Department of Hematology and Immunotherapy of Lu Daopei Hospital (Deputy Dean level), Director of the HLA Matching Room, Doctor of Hematology, Chinese Anti-Cancer Association, Member of the Hematopoietic Stem Cell Transplant and Cell Therapy Group of the Fifth Hematological Oncology Committee of the Chinese Medical Doctor Association Member of the Fifth Committee of the Branch of Hematologists Member of the Cell Research and Therapeutics Professional Committee of the Chinese Research Hospital Association Member of the Expert Group of the Human Tissue Antigen Professional Society of the Chinese Blood Transfusion Association Member of the Disease Professional Committee Member of the Lymphoma Professional Committee of Hebei Hematology Society
.
Recently, the world's premier scientific exchange event in the field of hematology-the American Society of Hematology (ASH) annual meeting is about to be held, and many clinical research results of Lu Daopei Hospital focusing on key issues of CAR-T therapy have once again appeared at the ASH annual meeting
.
On the occasion of the ASH meeting, Yimaitong was fortunate to invite Professor Zhang Xian from the Department of Hematology of Lu Daopei Hospital to share her outstanding research results in the field of CAR-T treatment, which are summarized as follows
.
Yimaitong: Many literatures show that TP53 mutation is a bad prognostic factor for CAR-T products in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).
Can you analyze this? Professor Zhang Xian now has a lot of CAR-T products targeting CD19, and the curative effect is also very good
.
There are more than 1,000 patients with relapsed/refractory B-ALL who received CD19 CAR-T therapy in the single center of Lu Daopei Hospital alone.
We have accumulated a lot of treatment experience
.
In the past two years, two summary analyses of CART treatment in 110 and 254 patients with relapsed/refractory B-ALL in our hospital showed that although the CD19 CAR-T complete remission rate was as high as 90%
.
However, the complete remission rate and long-term survival rate of patients with TP53 mutation and chromosome 17p deletion are lower than those without TP53 mutation and chromosome 17 abnormality.
Whether it is univariate analysis or multivariate analysis, it is confirmed to be independent Poor prognostic factors
.
Further analysis found that even in patients with TP53 mutation and chromosome 17p deletion, the complete remission rate after CD19 CART is as high as 78%, and long-term survival can reach more than 30%
.
In order to further analyze the factors affecting the efficacy of CD19 CAR-T in the TP53 mutation patient group, we screened 64 cases of TP53 mutation and/or from more than 400 patients with relapsed/refractory B-ALL who received CD19 CAR-T therapy.
In patients with chromosome 17p deletion, we analyzed nearly 20 factors that may affect TP53 gene abnormalities that have been reported in the literature.
Finally, it was found that other complex chromosomal abnormalities combined with CAR-T therapy did not bridge allogeneic hematopoietic stem cell transplantation (allo-HSCT).
) Is a very clear independent poor prognostic factor
.
Some other factors can also see the trend of impact on the prognosis, but no statistical difference has been observed in the current sample of 64 cases, and it needs to be observed and counted after further increasing the number of cases
.
Yimaitong: In the treatment of acute leukemia, what is the difference between CD7 CAR-T and CD19 CAR-T? Professor Zhang Xian our hospital started clinical trials of CD7 CAR-T cell therapy in October last year
.
The enrollment was mainly T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) patients, as well as some mature T-cell lymphoma patients
.
Because this patient population is relatively smaller than B-ALL and B-cell lymphoma patients, so far, there are about 70 patients receiving CD7 CAR-T therapy in our hospital
.
Our analysis found that the clinical characteristics of CD7 CAR-T after infusion are very different from those of CD19 CAR-T
.
The heat peak appears earlier after CD7 CAR-T reinfusion, and it is a double heat peak phenomenon
.
Fever will appear in the first 3 days after CD7 CAR-T cell reinfusion, and after a period of calm, there will be a fever peak in 10-21 days
.
The fever peak of CD19 CAR-T is basically in the 7-14 days after CAR-T infusion
.
Therefore, compared with patients who received CD19 CAR-T cells, patients who received CD7 CAR-T cells need to pay more attention to the side effects of CART
.
Except for the different characteristics of fever, there is no significant difference in the incidence of cytokine release syndrome (CRS) and CART-related neurotoxicity after CD7 CAR-T reinfusion compared with the incidence after CD19 CART treatment
.
Yimaitong: Can patients with CD7-positive acute mixed cell leukemia benefit from CD7 CAR-T treatment? How safe is it? Professor Zhang Xian Acute mixed cell leukemia is a rare subtype of acute leukemia that expresses multi-lineage differentiation antigens.
The prognosis is generally poor.
Relapsed/refractory acute mixed cell leukemia has a worse effect of chemotherapy.
Allogeneic hematopoietic stem cell transplantation The prognosis is not ideal, and there is a lack of very effective treatments before CAR-T
.
Based on the above background, we carried out the first clinical study on the treatment of relapsed/refractory acute mixed cell leukemia with CD7 CAR-T therapy
.
It is clear that patients with CD7-positive acute mixed cell leukemia, and even patients who relapse after transplantation, can benefit from CD7 CAR-T therapy, and the safety is within controllable range
.
Although the number of cases is small, it brings hope of cure for this type of patients
.
Yimaitong: You have announced many cutting-edge results at international conferences in the past few years.
What supports you to achieve so many results? Professor Zhang Xian finds suitable treatment options for various relapsed and refractory patients to save one life after another.
This is what our doctors have been doing
.
We have produced many results recently because our Lu Daopei Hospital is a very good medical transformation platform
.
First of all, our hospital has always been patient-centered, and we are very willing to apply cutting-edge medical results and leading treatment methods to patients.
We are willing to seek various new and promising scientific research results to be quickly applied to the clinic, and to strive for new drugs for patients , Immunotherapy products
.
Secondly, we have rich experience in the treatment and management of blood diseases, which can guarantee the safety of patients to the greatest extent
.
Finally, we need to summarize these results and analyze the statistically significant results for academic summary
.
While our hospital continues to explore and innovate in the field of blood diseases, it has been constantly summing up, hoping to bring hope to more patients with blood diseases by sharing our experience
.
Conclusion The annual ASH annual meeting is the top academic conference in the field of global hematology
.
Lu Daopei Hospital has been shortlisted for the ASH annual meeting for consecutive years, fully demonstrating its academic achievements in the industry and also reflecting the recognition of Lu Daopei's medical team by global hematology authorities.
Its excellent test results have been widely praised by the international hematology community
.
It is hoped that this "Chinese power" will continue to explore and lead China's CAR-T therapy to the top of the world's academic world and benefit more patients with blood diseases
.
Professor Zhang Xian, Director of the Department of Hematology and Immunotherapy of Lu Daopei Hospital (Deputy Dean level), Director of the HLA Matching Room, Doctor of Hematology, Chinese Anti-Cancer Association, Member of the Hematopoietic Stem Cell Transplant and Cell Therapy Group of the Fifth Hematological Oncology Committee of the Chinese Medical Doctor Association Member of the Fifth Committee of the Branch of Hematologists Member of the Cell Research and Therapeutics Professional Committee of the Chinese Research Hospital Association Member of the Expert Group of the Human Tissue Antigen Professional Society of the Chinese Blood Transfusion Association Member of the Disease Professional Committee Member of the Lymphoma Professional Committee of Hebei Hematology Society
