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From March 20 to 21, 2021, the 4th China Lymphoma Individualized Treatment Conference and the 2021 Chinese Anti-Cancer Association Lymphoma Professional Committee Annual Meeting will be held online, and many blood experts will participate online and offline , To share the latest research results of hematology.
At this meeting, Professor Junning Cao from the Cancer Hospital of Fudan University gave a theme report on "Research Progress in Extranodal NK/T Cell Lymphoma".
Yimaitong organized the main contents as follows.
Extranodal NK/T cell lymphoma originates from NK cells or cytotoxic T cells and is closely related to EBV infection.
It is common with tissue necrosis and vascular destruction.
Extranodal NK/T cell lymphoma mainly occurs in the upper respiratory tract and digestive tract, and is most common in the nasal cavity.
Extranodal lesions of the digestive tract other than the upper respiratory tract can be found in the skin, soft tissue, testicles, digestive tract, etc.
, with a poor prognosis, and primary lymph nodes are rare.
The risk factor score of extranodal NK/T cell lymphoma mainly uses the PINK score, and the PINK-E score combines EBV-DNA positive indicators on the basis of the PINK score.
Non-nasal primary NK/T cell lymphoma has a poor prognosis.
A retrospective study in Japan included 31 centers with extranodal NK/T cell lymphoma treated with SMILE regimen (methotrexate, ifosfamide, L-asparaginase, etoposide) from 2000 to 2013 Cases, among the 358 patients included in the study, 47 cases (13%) were non-nasal primary cases.
Among them, the origin of skin and soft tissue was the most common, being 18 cases.
At a median follow-up of 5.
8 years, the 2-year overall survival (OS) rate for patients with primary nasal extranodal NK/T-cell lymphoma was 70%, and the 2-year OS rate for non-nasal primary patients was 34%.
Common genetic abnormalities in extranodal NK/T cell lymphoma include JAK3, STAT3, NF-κB and so on.
The incidence of extranodal NK/T cell lymphoma is related to the EBV virus.
The EBV virus can cause high PD-1 expression in patients with extranodal NK/T cell lymphoma, leading to immune escape.
Compared with other lymphomas, extranodal NK/T cell lymphoma has more tissue necrosis and more free EBV-DNA in peripheral blood.
The prognosis of patients can be judged by detecting free EBV-DNA status at baseline; EBV-DNA status can be used to predict remission status during treatment; EBV-DNA status can be used to predict disease recurrence during follow-up.
The treatment of extranodal NK/T cell lymphoma depends on the stage of the disease.
For stage I extranodal NK/T cell lymphoma, radiotherapy alone can achieve better remission.
For patients with locally advanced extranodal NK/T cell lymphoma, a sequential treatment model of induction chemotherapy + radiotherapy, radiotherapy + chemotherapy is usually adopted.
Concurrent radiotherapy and chemotherapy is also a feasible treatment mode, but the incidence of adverse reactions such as mucositis is relatively high.
For advanced and relapsed refractory NK/T cell lymphomas, currently the main chemotherapy regimens containing L-asparaginase or pegaspartase are combined chemotherapy, including SMILE regimens, L-GEMOX regimens (peasparaginase, gemcitabine, oxa Liplatin), DDGP program (dexamethasone, cisplatin, gemcitabine, pegaspase).
Autologous hematopoietic stem cell transplantation and allogeneic hematopoietic stem cell transplantation also have a certain status in the treatment of relapsed and refractory NK/T cell lymphoma.
The immunotherapy programs that have emerged in recent years have brought new treatment options for patients who have failed L-asparaginase therapy.
Research conducted in Japan in 2011 showed that the SMILE regimen in the treatment of NK/T cell lymphoma patients has a complete remission (CR) rate of 45% and a partial remission (PR) rate of 34%.
However, the duration of remission (DOR) brought by the SMILE regimen in this study is relatively short, which is not suitable for multi-course treatment.
At the same time, the intensity of the program is relatively high, the incidence of adverse events (AE) of grade ≥3 in the study is relatively high, and the patient's tolerance is poor.
The Sun Yat-sen University Cancer Center team has carried out research in recent years to explore the efficacy and safety of the L-GEMOX regimen in the treatment of NK/T cell lymphoma.
A total of 117 patients were enrolled in the study, and the median treatment cycle was 4 cycles.
At a median follow-up of 17 months, the 3-year progression-free survival (PFS) rate of NK/T-cell lymphoma patients reached 57.
8%, and the 3-year OS rate reached 72.
7%.
The current treatment plan has been included in many clinical guidelines such as NCCN and CSCO.
The team of Professor Zhang Mingzhi from the First Affiliated Hospital of Zhengzhou University compared the efficacy of the DDGP regimen and the SMILE regimen in the treatment of NK/T cell lymphoma.
The results of the study showed that the average treatment period was longer in the DDGP regimen group (5.
57 cycles vs 3.
9 cycles).
At a median follow-up of 14 months, the CR rate (71% vs 29%), 1-year OS rate (90% vs 57%), 1-year PFS rate (80% vs 38%), and 2-year OS rate in the DDGP regimen group were all Higher (74% vs 45%).
A retrospective study in South Korea showed that PD-L1 expression was 79.
7% in NK/T cell lymphoma cells and 78.
5% in immune cells; PD-1 expression was 1.
3% in NK/T cell lymphoma cells, and in immune cells.
The cells are 1.
4%.
In addition, the high expression of PD-L1 was associated with the low IPI score of patients with NK/T cell lymphoma (P=0.
044).
Professor Junning Cao then introduced the research progress of PD-1/PD-L1 monoclonal antibody in the treatment of relapsed and refractory NK/T cell lymphoma in recent years: a study on PD-1 monoclonal antibody pembrolizumab monotherapy The curative effect of relapsed and refractory NK/T cell lymphoma was explored.
The results of the study showed that at a median follow-up of 6 months, all 7 patients who received pembrolizumab monotherapy were effective, and 5 of them reached CR ; Tumor cells of 4 patients detected positive expression of PD-L1, of which 3 patients reached CR.
The phase II ORIENT-4 study explored the efficacy of the PD-1 monoclonal antibody sintilimab as a single agent in the treatment of NK/T cell lymphoma.
The results of the study reported at the 2020 ASCO conference showed that the objective response rate (ORR) of patients treated with sintilimab reached 67.
9%.
At a median follow-up of 26.
9 months, the 24-month OS rate reached 78.
6%, while the median OS did not reach.
In addition to the direct anti-tumor effect of the HDAC inhibitor Chidamide, it also has an immunomodulatory effect.
Previous studies have demonstrated the effectiveness of Chidamide in the treatment of relapsed and refractory NK/T cell lymphoma (ORR: 50%; CR) Rate: 25%).
A study was announced at the 2020 ASH Conference to explore the efficacy of Chidamide combined with Sintilizumab in NK/T cell lymphoma.
The results of the study showed: ORR of Sintilizumab combined with Chidamide Reached 58.
3%, the CR rate reached 44.
4%, and more than 50% of the patients had reduced tumor volume.
The combined program also improved the survival of NK/T-cell lymphoma patients.
The median DOR reached 9.
2 months, the 1-year OS rate reached 79.
1%, and the 1-year PFS rate reached 66%.
The study also found that the curative effect of NK/T cell lymphoma patients is correlated with the PD-L1 expression level of the patients.
Patients with PD-L1 expression ≥50% have a better prognosis after receiving the combined treatment.
Professor Junning Cao concluded: Extranodal NK/T cell lymphoma is a special type of lymphoma, which is mainly in Asia.
EBV infection is closely related to NK/T cell lymphoma, and the EBV-DNA load in peripheral blood can predict prognosis and judge tumor remission and tumor recurrence.
In limited-stage patients, the remission rate of sequential pegaspartase combined with chemotherapy and radiotherapy is higher, and some patients can be cured.
For advanced or relapsed patients, treatment is based on pegaspase combined with chemotherapy.
Commonly used regimens include L-GEMOX, DDGP, SMILE regimens and so on.
NK/T cell lymphoma cells highly express PD-L1, which is effective for immune checkpoint inhibitor therapy, but the remission rate and effective time report are inconsistent.
The anti-PD-1 monoclonal antibody combined with Chidamide has achieved good curative effect and lasting remission, and it is well tolerated.
At present, other new drug researches for NK/T cell lymphoma also involve anti-CD30 antibody conjugate drugs, JAK3 inhibitors and so on.
Professor Junning Cao, Deputy Director of the Lymphoma Specialist, Department of Oncology, Cancer Hospital of Fudan University, Deputy Chief Expert of Lymphoma Multidisciplinary, Chairman of the Lymphoma Professional Committee of the Shanghai Anti-Cancer Association, Standing Committee Member of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association Member of the Standing Committee of the Tumor Alliance Member of the Chinese Society of Clinical Oncology Member of the Chinese Anti-Cancer Association Clinical Chemotherapy Committee of the Chinese Medical Association Member of the Lymph Blood Group of the Chinese Medical Association Member of the Anti-tumor Drug Professional Committee of the Chinese Pharmaceutical Association Member, Vice-Chairman of the Lymphoma Professional Committee of China Association for Geriatric Health Care
At this meeting, Professor Junning Cao from the Cancer Hospital of Fudan University gave a theme report on "Research Progress in Extranodal NK/T Cell Lymphoma".
Yimaitong organized the main contents as follows.
Extranodal NK/T cell lymphoma originates from NK cells or cytotoxic T cells and is closely related to EBV infection.
It is common with tissue necrosis and vascular destruction.
Extranodal NK/T cell lymphoma mainly occurs in the upper respiratory tract and digestive tract, and is most common in the nasal cavity.
Extranodal lesions of the digestive tract other than the upper respiratory tract can be found in the skin, soft tissue, testicles, digestive tract, etc.
, with a poor prognosis, and primary lymph nodes are rare.
The risk factor score of extranodal NK/T cell lymphoma mainly uses the PINK score, and the PINK-E score combines EBV-DNA positive indicators on the basis of the PINK score.
Non-nasal primary NK/T cell lymphoma has a poor prognosis.
A retrospective study in Japan included 31 centers with extranodal NK/T cell lymphoma treated with SMILE regimen (methotrexate, ifosfamide, L-asparaginase, etoposide) from 2000 to 2013 Cases, among the 358 patients included in the study, 47 cases (13%) were non-nasal primary cases.
Among them, the origin of skin and soft tissue was the most common, being 18 cases.
At a median follow-up of 5.
8 years, the 2-year overall survival (OS) rate for patients with primary nasal extranodal NK/T-cell lymphoma was 70%, and the 2-year OS rate for non-nasal primary patients was 34%.
Common genetic abnormalities in extranodal NK/T cell lymphoma include JAK3, STAT3, NF-κB and so on.
The incidence of extranodal NK/T cell lymphoma is related to the EBV virus.
The EBV virus can cause high PD-1 expression in patients with extranodal NK/T cell lymphoma, leading to immune escape.
Compared with other lymphomas, extranodal NK/T cell lymphoma has more tissue necrosis and more free EBV-DNA in peripheral blood.
The prognosis of patients can be judged by detecting free EBV-DNA status at baseline; EBV-DNA status can be used to predict remission status during treatment; EBV-DNA status can be used to predict disease recurrence during follow-up.
The treatment of extranodal NK/T cell lymphoma depends on the stage of the disease.
For stage I extranodal NK/T cell lymphoma, radiotherapy alone can achieve better remission.
For patients with locally advanced extranodal NK/T cell lymphoma, a sequential treatment model of induction chemotherapy + radiotherapy, radiotherapy + chemotherapy is usually adopted.
Concurrent radiotherapy and chemotherapy is also a feasible treatment mode, but the incidence of adverse reactions such as mucositis is relatively high.
For advanced and relapsed refractory NK/T cell lymphomas, currently the main chemotherapy regimens containing L-asparaginase or pegaspartase are combined chemotherapy, including SMILE regimens, L-GEMOX regimens (peasparaginase, gemcitabine, oxa Liplatin), DDGP program (dexamethasone, cisplatin, gemcitabine, pegaspase).
Autologous hematopoietic stem cell transplantation and allogeneic hematopoietic stem cell transplantation also have a certain status in the treatment of relapsed and refractory NK/T cell lymphoma.
The immunotherapy programs that have emerged in recent years have brought new treatment options for patients who have failed L-asparaginase therapy.
Research conducted in Japan in 2011 showed that the SMILE regimen in the treatment of NK/T cell lymphoma patients has a complete remission (CR) rate of 45% and a partial remission (PR) rate of 34%.
However, the duration of remission (DOR) brought by the SMILE regimen in this study is relatively short, which is not suitable for multi-course treatment.
At the same time, the intensity of the program is relatively high, the incidence of adverse events (AE) of grade ≥3 in the study is relatively high, and the patient's tolerance is poor.
The Sun Yat-sen University Cancer Center team has carried out research in recent years to explore the efficacy and safety of the L-GEMOX regimen in the treatment of NK/T cell lymphoma.
A total of 117 patients were enrolled in the study, and the median treatment cycle was 4 cycles.
At a median follow-up of 17 months, the 3-year progression-free survival (PFS) rate of NK/T-cell lymphoma patients reached 57.
8%, and the 3-year OS rate reached 72.
7%.
The current treatment plan has been included in many clinical guidelines such as NCCN and CSCO.
The team of Professor Zhang Mingzhi from the First Affiliated Hospital of Zhengzhou University compared the efficacy of the DDGP regimen and the SMILE regimen in the treatment of NK/T cell lymphoma.
The results of the study showed that the average treatment period was longer in the DDGP regimen group (5.
57 cycles vs 3.
9 cycles).
At a median follow-up of 14 months, the CR rate (71% vs 29%), 1-year OS rate (90% vs 57%), 1-year PFS rate (80% vs 38%), and 2-year OS rate in the DDGP regimen group were all Higher (74% vs 45%).
A retrospective study in South Korea showed that PD-L1 expression was 79.
7% in NK/T cell lymphoma cells and 78.
5% in immune cells; PD-1 expression was 1.
3% in NK/T cell lymphoma cells, and in immune cells.
The cells are 1.
4%.
In addition, the high expression of PD-L1 was associated with the low IPI score of patients with NK/T cell lymphoma (P=0.
044).
Professor Junning Cao then introduced the research progress of PD-1/PD-L1 monoclonal antibody in the treatment of relapsed and refractory NK/T cell lymphoma in recent years: a study on PD-1 monoclonal antibody pembrolizumab monotherapy The curative effect of relapsed and refractory NK/T cell lymphoma was explored.
The results of the study showed that at a median follow-up of 6 months, all 7 patients who received pembrolizumab monotherapy were effective, and 5 of them reached CR ; Tumor cells of 4 patients detected positive expression of PD-L1, of which 3 patients reached CR.
The phase II ORIENT-4 study explored the efficacy of the PD-1 monoclonal antibody sintilimab as a single agent in the treatment of NK/T cell lymphoma.
The results of the study reported at the 2020 ASCO conference showed that the objective response rate (ORR) of patients treated with sintilimab reached 67.
9%.
At a median follow-up of 26.
9 months, the 24-month OS rate reached 78.
6%, while the median OS did not reach.
In addition to the direct anti-tumor effect of the HDAC inhibitor Chidamide, it also has an immunomodulatory effect.
Previous studies have demonstrated the effectiveness of Chidamide in the treatment of relapsed and refractory NK/T cell lymphoma (ORR: 50%; CR) Rate: 25%).
A study was announced at the 2020 ASH Conference to explore the efficacy of Chidamide combined with Sintilizumab in NK/T cell lymphoma.
The results of the study showed: ORR of Sintilizumab combined with Chidamide Reached 58.
3%, the CR rate reached 44.
4%, and more than 50% of the patients had reduced tumor volume.
The combined program also improved the survival of NK/T-cell lymphoma patients.
The median DOR reached 9.
2 months, the 1-year OS rate reached 79.
1%, and the 1-year PFS rate reached 66%.
The study also found that the curative effect of NK/T cell lymphoma patients is correlated with the PD-L1 expression level of the patients.
Patients with PD-L1 expression ≥50% have a better prognosis after receiving the combined treatment.
Professor Junning Cao concluded: Extranodal NK/T cell lymphoma is a special type of lymphoma, which is mainly in Asia.
EBV infection is closely related to NK/T cell lymphoma, and the EBV-DNA load in peripheral blood can predict prognosis and judge tumor remission and tumor recurrence.
In limited-stage patients, the remission rate of sequential pegaspartase combined with chemotherapy and radiotherapy is higher, and some patients can be cured.
For advanced or relapsed patients, treatment is based on pegaspase combined with chemotherapy.
Commonly used regimens include L-GEMOX, DDGP, SMILE regimens and so on.
NK/T cell lymphoma cells highly express PD-L1, which is effective for immune checkpoint inhibitor therapy, but the remission rate and effective time report are inconsistent.
The anti-PD-1 monoclonal antibody combined with Chidamide has achieved good curative effect and lasting remission, and it is well tolerated.
At present, other new drug researches for NK/T cell lymphoma also involve anti-CD30 antibody conjugate drugs, JAK3 inhibitors and so on.
Professor Junning Cao, Deputy Director of the Lymphoma Specialist, Department of Oncology, Cancer Hospital of Fudan University, Deputy Chief Expert of Lymphoma Multidisciplinary, Chairman of the Lymphoma Professional Committee of the Shanghai Anti-Cancer Association, Standing Committee Member of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association Member of the Standing Committee of the Tumor Alliance Member of the Chinese Society of Clinical Oncology Member of the Chinese Anti-Cancer Association Clinical Chemotherapy Committee of the Chinese Medical Association Member of the Lymph Blood Group of the Chinese Medical Association Member of the Anti-tumor Drug Professional Committee of the Chinese Pharmaceutical Association Member, Vice-Chairman of the Lymphoma Professional Committee of China Association for Geriatric Health Care
