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Lymphocytic disease is currently one of the most vigorous fields in hematology at home and abroad.
In recent years, remarkable achievements have been made in the pathogenesis of the disease to targeted and immunotherapy.
In order to promote domestic and international peer exchanges, the First National Lymphocytic Disease Academic Conference of the Chinese Medical Association and the 2021 International Lymphoma Update Symposium will be held on April 16-18, 2021.
The conference specially invited well-known experts at home and abroad to give wonderful speeches, covering many aspects of lymphocytic diseases.
Yimaitong was fortunate to invite Professor Xu Wei from the First Affiliated Hospital of Nanjing Medical University to share the current status of the use of BCL-2 inhibitors in chronic lymphocytic leukemia and the research progress of drug resistance.
Professor Xu Wei, Chief Physician, PhD Supervisor, Deputy Director of the Department of Hematology, First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People's Hospital), Deputy Chairman of the Hematology Oncology Committee of the Chinese Anti-Cancer Association, and Leader of the Lymphoma Group, China Association for Geriatric Health Care Lymphoma Professional Committee Vice Chairman CSCO China Anti-Lymphoma Alliance Standing Committee Member of the Standing Committee of the Chinese Society of Geriatrics Hematology Branch Member of the Standing Committee of the Chinese Association of Women Doctors Member of the Experimental Hematology Professional Committee of the Pathophysiology Society Member and Secretary of the Integrated Hematology Professional Committee of the Chinese Medical Doctor Association Integrative Medicine Physician Branch Deputy Chairman of the Hematology Society of Jiangsu Medical Association Vice Chairman of the Lymphoma Professional Committee of Jiangsu Research Hospital Association Chairman of the Lymphoma Alliance, Vice Chairman of the Hematological Oncology Committee of Jiangsu Anti-Cancer Association, Member of the Standing Committee of the Lymphoma Professional Committee of Jiangsu Anti-Cancer Association, Vice Chairman of Nanjing Society of Hematology, Chinese Journal of Hematology, Chinese Journal of Experimental Hematology, and Editors of International Journal of Blood Transfusion and Hematology, "Leukemia·Lymphoma" and "BLOOD Chinese Edition" and other journals Yi Maitong: BCL-2 inhibitors are currently attracting attention in the field of hematological tumors, of which BCL-2 inhibitors Venecla has been approved for the treatment of acute myeloid leukemia (AML) in China.
In addition to the approved AML, what is the current status of the use of BCL-2 inhibitors in other hematological tumors? Professor Xu Wei's BCL-2 inhibitors are a hot topic in the field of hematological tumors.
Currently, BCL-2 inhibitors have shown good efficacy in a number of clinical studies, and the representative drug is Venecla.
Relevant studies have shown that Venecla can achieve long-lasting and deep relief for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del(17p) and complex karyotypes.
At present, the FDA has approved Venecla and anti-CD20 monoclonal antibody as one of the standard treatments for CLL.
The approval of Venecla is based on the results of the Phase III CLL14 study.
The study compared the efficacy of venekra combined with anti-CD20 monoclonal antibody otuzumab and chlorambucil combined with otuzumab in newly-treated CLL patients with comorbidities.
At a median follow-up of 39.
6 months in the study, the 3-year progression-free survival (PFS) rate of the Venecla group reached 81.
9%, which was better than the 3-year PFS rate of 49.
5% in the chlorambucil group; the periphery of the Venecla group The negative rate of minimal residual disease (MRD) is also higher (76% vs 35%).
In addition to the CLL14 study, the phase III MURANO study also demonstrated the excellent efficacy of Venecla in CLL.
This study compared the efficacy of venacral combined with rituximab and bendamustine combined with rituximab in patients with relapsed and refractory CLL.
At a median follow-up of 59 months, the PFS rate in the Venecla group was higher (53.
6% vs 17%).
Subgroup analysis showed that for CLL patients with TP53 mutations, the Venecla combined regimen also showed a better efficacy.
In addition, the combination of BCL-2 inhibitors also shows a good therapeutic prospect in other hematological tumors.
The phase II CAVALLI study explored the efficacy of BCL-2 inhibitors combined with standard R-CHOP regimens in patients with diffuse large B-cell lymphoma.
The results of the study showed that the combined regimen can improve the efficacy of patients with BCL-2 translocations. Yimaitong: Resistance is also a common problem in the clinical treatment of CLL with BCL-2 inhibitors.
Could you please introduce how to deal with the resistance of BCL-2 inhibitors? Regarding the resistance of BCL-2 inhibitors, what are the current research developments worthy of attention? Professor Xu Wei's resistance to BCL-2 inhibitors in CLL may be related to the disease itself.
For CLL patients with BAX/BAK loss and TP53 loss, BCL-2 inhibitors are less effective.
G101V mutations in the BCL2 gene after treatment with BCL-2 inhibitors in some patients can also lead to drug resistance.
In addition, the high expression of anti-apoptotic proteins in the signaling pathway is also associated with the resistance of BCL-2 inhibitors.
At present, related studies have also explored the treatment options for CLL patients after resistance to BCL-2 inhibitors.
In the phase Ib clinical trial of the MURANO study, 4 patients with CLL developed disease progression after the withdrawal of Veneclair.
Among them, 3 patients achieved remission after receiving Veneclair again, and 2 patients achieved sustained remission.
In the phase III clinical trial of the MURANO study, 11 patients also received Venecla treatment after disease progression, and 6 patients achieved remission, with an objective remission rate (ORR) of 55%.
For patients who are resistant to BCL-2 inhibitors, re-activating BCL-2 inhibitors is a viable treatment option.
BTK inhibitors and PI3K inhibitors are also optional therapeutic drugs for CLL patients who are resistant to BCL-2 inhibitors.
International multi-center retrospective studies have shown that BTK inhibitors are the most commonly used follow-up treatment for CLL patients who are resistant to BCL-2 inhibitors.
For CLL patients who have not been treated with BTK inhibitors, the median PFS is expected to reach 32 months.
The efficacy of PI3K inhibitors in these patients is relatively inferior.
Relevant studies have shown that for CLL patients who have not received PI3K inhibitors and are resistant to BCL-2 inhibitors, the ORR of PI3K inhibitors is 46.
9%; median follow-up At 5 months, the median PFS reached 5 months. Cell therapy is also a viable treatment option for patients with CLL who are resistant to BCL-2 inhibitors.
A multi-center retrospective study showed that the 2-year overall survival (OS) rate of patients with relapsed and refractory CLL receiving allogeneic hematopoietic stem cell transplantation reached 82%, and the 2-year PFS rate reached 60%.
Another study explored the efficacy of chimeric antigen receptor cellular immunotherapy (CAR-T) in patients with relapsed and refractory CLL.
The results of the study showed that the ORR of CAR-T treatment for relapsed and refractory CLL reached 66.
6%, 33.
3% The patient achieved complete remission (CR).
However, for CLL patients who have undergone disease progression after treatment with BCL-2 inhibitors after multiple treatments, there is currently no evidence to support the use of chemotherapy or immunotherapy again.
For patients with relapsed and refractory CLL who have never received chemotherapy or immunotherapy, the effect of using traditional chemotherapy or immunotherapy again, there is currently no research involved.
For this type of patients, if accompanied by IGHV mutations, chemotherapy or immunotherapy can be considered.
At present, the research on the resistance mechanism of BCL-2 inhibitors is still relatively superficial.
It is expected that with the widespread application of BCL-2 inhibitors in the future, we will further explore the resistance mechanism of BCL-2 inhibitors and find a more suitable BCL-2 The treatment options for inhibitor-resistant patients will benefit these patients.
Poke "read the original text" and we will make progress together
In recent years, remarkable achievements have been made in the pathogenesis of the disease to targeted and immunotherapy.
In order to promote domestic and international peer exchanges, the First National Lymphocytic Disease Academic Conference of the Chinese Medical Association and the 2021 International Lymphoma Update Symposium will be held on April 16-18, 2021.
The conference specially invited well-known experts at home and abroad to give wonderful speeches, covering many aspects of lymphocytic diseases.
Yimaitong was fortunate to invite Professor Xu Wei from the First Affiliated Hospital of Nanjing Medical University to share the current status of the use of BCL-2 inhibitors in chronic lymphocytic leukemia and the research progress of drug resistance.
Professor Xu Wei, Chief Physician, PhD Supervisor, Deputy Director of the Department of Hematology, First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People's Hospital), Deputy Chairman of the Hematology Oncology Committee of the Chinese Anti-Cancer Association, and Leader of the Lymphoma Group, China Association for Geriatric Health Care Lymphoma Professional Committee Vice Chairman CSCO China Anti-Lymphoma Alliance Standing Committee Member of the Standing Committee of the Chinese Society of Geriatrics Hematology Branch Member of the Standing Committee of the Chinese Association of Women Doctors Member of the Experimental Hematology Professional Committee of the Pathophysiology Society Member and Secretary of the Integrated Hematology Professional Committee of the Chinese Medical Doctor Association Integrative Medicine Physician Branch Deputy Chairman of the Hematology Society of Jiangsu Medical Association Vice Chairman of the Lymphoma Professional Committee of Jiangsu Research Hospital Association Chairman of the Lymphoma Alliance, Vice Chairman of the Hematological Oncology Committee of Jiangsu Anti-Cancer Association, Member of the Standing Committee of the Lymphoma Professional Committee of Jiangsu Anti-Cancer Association, Vice Chairman of Nanjing Society of Hematology, Chinese Journal of Hematology, Chinese Journal of Experimental Hematology, and Editors of International Journal of Blood Transfusion and Hematology, "Leukemia·Lymphoma" and "BLOOD Chinese Edition" and other journals Yi Maitong: BCL-2 inhibitors are currently attracting attention in the field of hematological tumors, of which BCL-2 inhibitors Venecla has been approved for the treatment of acute myeloid leukemia (AML) in China.
In addition to the approved AML, what is the current status of the use of BCL-2 inhibitors in other hematological tumors? Professor Xu Wei's BCL-2 inhibitors are a hot topic in the field of hematological tumors.
Currently, BCL-2 inhibitors have shown good efficacy in a number of clinical studies, and the representative drug is Venecla.
Relevant studies have shown that Venecla can achieve long-lasting and deep relief for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del(17p) and complex karyotypes.
At present, the FDA has approved Venecla and anti-CD20 monoclonal antibody as one of the standard treatments for CLL.
The approval of Venecla is based on the results of the Phase III CLL14 study.
The study compared the efficacy of venekra combined with anti-CD20 monoclonal antibody otuzumab and chlorambucil combined with otuzumab in newly-treated CLL patients with comorbidities.
At a median follow-up of 39.
6 months in the study, the 3-year progression-free survival (PFS) rate of the Venecla group reached 81.
9%, which was better than the 3-year PFS rate of 49.
5% in the chlorambucil group; the periphery of the Venecla group The negative rate of minimal residual disease (MRD) is also higher (76% vs 35%).
In addition to the CLL14 study, the phase III MURANO study also demonstrated the excellent efficacy of Venecla in CLL.
This study compared the efficacy of venacral combined with rituximab and bendamustine combined with rituximab in patients with relapsed and refractory CLL.
At a median follow-up of 59 months, the PFS rate in the Venecla group was higher (53.
6% vs 17%).
Subgroup analysis showed that for CLL patients with TP53 mutations, the Venecla combined regimen also showed a better efficacy.
In addition, the combination of BCL-2 inhibitors also shows a good therapeutic prospect in other hematological tumors.
The phase II CAVALLI study explored the efficacy of BCL-2 inhibitors combined with standard R-CHOP regimens in patients with diffuse large B-cell lymphoma.
The results of the study showed that the combined regimen can improve the efficacy of patients with BCL-2 translocations. Yimaitong: Resistance is also a common problem in the clinical treatment of CLL with BCL-2 inhibitors.
Could you please introduce how to deal with the resistance of BCL-2 inhibitors? Regarding the resistance of BCL-2 inhibitors, what are the current research developments worthy of attention? Professor Xu Wei's resistance to BCL-2 inhibitors in CLL may be related to the disease itself.
For CLL patients with BAX/BAK loss and TP53 loss, BCL-2 inhibitors are less effective.
G101V mutations in the BCL2 gene after treatment with BCL-2 inhibitors in some patients can also lead to drug resistance.
In addition, the high expression of anti-apoptotic proteins in the signaling pathway is also associated with the resistance of BCL-2 inhibitors.
At present, related studies have also explored the treatment options for CLL patients after resistance to BCL-2 inhibitors.
In the phase Ib clinical trial of the MURANO study, 4 patients with CLL developed disease progression after the withdrawal of Veneclair.
Among them, 3 patients achieved remission after receiving Veneclair again, and 2 patients achieved sustained remission.
In the phase III clinical trial of the MURANO study, 11 patients also received Venecla treatment after disease progression, and 6 patients achieved remission, with an objective remission rate (ORR) of 55%.
For patients who are resistant to BCL-2 inhibitors, re-activating BCL-2 inhibitors is a viable treatment option.
BTK inhibitors and PI3K inhibitors are also optional therapeutic drugs for CLL patients who are resistant to BCL-2 inhibitors.
International multi-center retrospective studies have shown that BTK inhibitors are the most commonly used follow-up treatment for CLL patients who are resistant to BCL-2 inhibitors.
For CLL patients who have not been treated with BTK inhibitors, the median PFS is expected to reach 32 months.
The efficacy of PI3K inhibitors in these patients is relatively inferior.
Relevant studies have shown that for CLL patients who have not received PI3K inhibitors and are resistant to BCL-2 inhibitors, the ORR of PI3K inhibitors is 46.
9%; median follow-up At 5 months, the median PFS reached 5 months. Cell therapy is also a viable treatment option for patients with CLL who are resistant to BCL-2 inhibitors.
A multi-center retrospective study showed that the 2-year overall survival (OS) rate of patients with relapsed and refractory CLL receiving allogeneic hematopoietic stem cell transplantation reached 82%, and the 2-year PFS rate reached 60%.
Another study explored the efficacy of chimeric antigen receptor cellular immunotherapy (CAR-T) in patients with relapsed and refractory CLL.
The results of the study showed that the ORR of CAR-T treatment for relapsed and refractory CLL reached 66.
6%, 33.
3% The patient achieved complete remission (CR).
However, for CLL patients who have undergone disease progression after treatment with BCL-2 inhibitors after multiple treatments, there is currently no evidence to support the use of chemotherapy or immunotherapy again.
For patients with relapsed and refractory CLL who have never received chemotherapy or immunotherapy, the effect of using traditional chemotherapy or immunotherapy again, there is currently no research involved.
For this type of patients, if accompanied by IGHV mutations, chemotherapy or immunotherapy can be considered.
At present, the research on the resistance mechanism of BCL-2 inhibitors is still relatively superficial.
It is expected that with the widespread application of BCL-2 inhibitors in the future, we will further explore the resistance mechanism of BCL-2 inhibitors and find a more suitable BCL-2 The treatment options for inhibitor-resistant patients will benefit these patients.
Poke "read the original text" and we will make progress together
