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In recent years, the treatment of hematological tumors has been changing with each passing day, and significant progress has been made in both theory and clinical practice.
In order to further improve the level of diagnosis and treatment of lymphoma in my country, the CSCO Anti-Lymphoma Alliance Tour-Tianjin Station Conference will be held on March 27, 2021.
This conference is based on the clinic, focusing on the frontier progress of lymphoma, and discussing the diagnosis and treatment of lymphoma in depth.
At this conference, Yimaitong was fortunate to interview Professor Qian Zhengzi from Tianjin Medical University Cancer Hospital to share the current status of diagnosis and treatment of Hodgkin’s Lymphoma (HL) and the latest progress.
Professor Qian Zhengzi, Associate Chief Physician, Doctor of Oncology CSCO Head and Neck Tumor Professional Committee Member, Tianjin Anti-Cancer Association Lymphoma Professional Committee Standing Committee Member of "Leukemia-Lymphoma" Journal Editor Yi Maitong: Could you please introduce me, Hodgkin What is the current status of diagnosis and treatment of lymphoma (HL)? Are there unmet clinical needs? Professor Qian Zhengzi The incidence of Hodgkin's Lymphoma (HL) in my country is relatively low, accounting for about 9% of all lymphoma subtypes, far below the level of 30% in European and American countries.
Most HL patients in my country are classical Hodgkin lymphoma (cHL), accounting for about 95%.
The prognosis of HL is relatively good, the 5-year survival rate is about 80%-90%, and most HL patients can achieve better survival after first-line treatment.
Relapsed and refractory cHL is currently mainly treated with salvage chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) for consolidation therapy, and the curative effect is relatively good.
However, there are still many unmet clinical needs for HL.
After the first-line ABVD chemotherapy of cHL patients, the 5-year failure-free survival (FFS) rate is only 70%, and 30% of patients will relapse and refractory.
Among them, 5%-9% of patients are primary refractory, and 10%-20% of patients will relapse.
As there is still a lack of mature and effective molecular markers, how to screen out these relapsed and refractory patients at the initial stage of treatment is a difficult problem for HL treatment.
A study explored the IHL30 model that included 18 genetic testing of the HL tumor microenvironment.
The results of the study showed that the FFS rate of patients with high scores under this model was only 41%, and the FFS rate of patients with low scores could reach 92%, but the two groups There was no significant difference in the overall survival (OS) of the patients.
Considering that genetic testing has not yet been widely carried out, the clinical application of this model is still facing some difficulties, and it is necessary to explore a more simplified HL prognosis model in clinical practice.
Another unmet need for treatment of HL is the efficacy of conventional second-line salvage treatment.
At present, the efficacy of conventional second-line chemotherapy for HL is limited, with a complete remission (CR) rate of about 20%-50%.
Very few patients can receive ASCT consolidation therapy.
At present, it is necessary to explore more new drugs to increase the CR rate of second-line salvage chemotherapy for HL patients, so that more HL patients can successfully bridge ASCT.
In addition, the trade-off between long-term efficacy and long-term survival of HL is also an unmet clinical need.
The current treatment of HL is based on chemotherapy, mainly using ABVD regimen, enhanced BEACOP regimen and other chemotherapy regimens.
Although intensive chemotherapy can bring better curative effects, it also brings toxic side effects such as reproductive toxicity, cardiotoxicity, pulmonary toxicity, and second primary tumors to HL patients.
Therefore, it is necessary to screen out HL patients with better prognosis in clinical practice, reduce the intensity and cycle of chemotherapy in these patients, and reduce toxic and side effects; at the same time, for patients with poor prognosis, they can be combined with other individualized treatments on the basis of intensive treatment to improve The patient's cure is possible.
At present, the adjustment of clinical treatment strategies for HL still depends on the guidance of mid-term PET-CT detection.
The AHL2011 study explored the adjustment of the HL treatment strategy guided by the PET-CT test.
The study of patients with advanced HL received 6 cycles of intensive BEACOP treatment, and PET-CT testing was performed after the second and fourth cycles of treatment.
PET- The follow-up treatment plan for patients with negative CT test was adjusted to ABVD plan.
The long-term follow-up results of the study showed that patients with negative PET-CT tests after the second and fourth cycles of treatment had better progression-free survival (PFS) and OS than those with positive PET-CT tests after the second and fourth cycles of treatment; 2.
The adjustment of treatment strategy after 4 cycles did not affect the survival of HL patients, and at the same time reduced the incidence of secondary primary tumors, infertility, thrombocytopenia ≥3 grade, and anemia in HL patients.
PET-CT detection is still an important guide for the adjustment of the current HL treatment plan.
Yimaitong: In recent years, great progress has been made in the field of lymphoma treatment.
Can you sum up and review for us, what new progress has been made in the field of classic HL diagnosis and treatment? Professor Qian Zhengzi has seen many new drugs in the field of HL treatment in recent years.
Whether it is an immunotherapeutic drug represented by antibody-conjugated drugs (ADC) verbutuximab (BV) and various PD-1 inhibitors, or targeted drugs represented by nalidomide and bendamustine Both have achieved good results.
At present, the application of BV in the treatment of HL is relatively mature and has been indicated for HL in many countries/regions.
The ECHELON-1 study compared the efficacy of BV combined with AVD regimen and ABVD regimen in newly treated advanced HL patients.
The long-term follow-up results showed that the 5-year PFS rate of the BV group was significantly better than that of the ABVD group (3-year PFS rate: 83.
1% vs 76.
0%; HR: 0.
70; P=0.
005).
The results of the study announced at the 2019 ASH Conference showed that the complete metabolic remission (CMR) rate of second-line patients with relapsed and refractory HL after receiving BV combined with ICE salvage chemotherapy can reach 69.
2%, which is a better bridge to ASCT.
In addition, BV can also be used for maintenance treatment of high-risk HL patients after ASCT to improve PFS.
For older HL patients who cannot tolerate chemotherapy, the treatment of the BV single-drug combination regimen can also improve the efficacy of the patient, reduce the side effects, and improve the quality of life of the patient.
PD-1 inhibitors are also relatively mature drugs in the treatment of HL, and have been included in the NCCN guidelines as a treatment recommendation for relapsed and refractory HL.
At present, the overall effective rate (ORR) of PD-1 inhibitors in the treatment of HL is about 60%-80%, but the CR rate is relatively low.
Among them, tislelizumab, which has been on the market in recent years, has an excellent effect on HL, with a CR rate of 61%.
The KEYNOTE-204 study compared the efficacy of PD-1 inhibitor pembrolizumab and BV in relapsed and refractory cHL.
The results of the study showed that the PFS of the pembrolizumab group was better than that of the BV group, reaching 13.
2 month.
Another study explored the efficacy of pembrolizumab combined with BVD regimen in relapsed and refractory cHL.
The results of the study showed that the CR rate of the combined regimen was as high as 95%, and the ORR reached 100%.
This joint solution can bring deep relief to cHL and is also suitable for bridging ASCT.
In addition to pembrolizumab, the PD-1 inhibitor nivolizumab also showed good efficacy in HL.
The Checkmate-205 study explored the efficacy of nivolumab combined with AVD in patients with advanced cHL.
The results of the study showed that the ORR of the program in cHL patients reached 86%, the CMR rate reached 75%, and the efficacy was considerable.
For patients who relapse after ASCT or who are not suitable for ASCT, it is recommended to receive PD-1 inhibitor treatment.
Related studies have also explored the advancement of PD-1 inhibitors in the treatment of HL.
A study released in 2020 explored the early stages of poor prognosis of the PD-1 inhibitor nivolumab combined with AVD regimen in simultaneous or sequential treatment.
The curative effect of cHL, the results of the study showed: the CR rate of this program reached 90%, and after a median follow-up of 2 years, the 2-year PFS rate of cHL patients reached 98%, and the 2-year OS rate reached 100%.
PD-1 inhibitors also have certain potential in the first-line treatment of HL.
The combination of BV and PD-1 inhibitors is also a research hotspot in the treatment of HL.
The Checkmate-744 study explored the efficacy of BV combined with nivolumab and bendamustine in patients with relapsed and refractory cHL aged 5-30 years.
The results of the study showed that the CMR of the combined program can reach 88%.
Well tolerated.
Another study explored the efficacy of BV combined with nivolumab in the maintenance treatment of high-risk HL patients after ASCT.
The results of the study showed that: 6 patients who did not reach CR after ASCT received BV combined with nivolumab, 5 cases The patients subsequently reached CR status, and the combined program significantly improved the PFS of HL patients.
Professor Han Weidong of my country explored the efficacy of PD-1 inhibitor carrelizumab combined with epigenetic drug decitabine in relapsed and refractory cHL.
The results of the study showed that the CR rate of the combined regimen reached 71%.
The addition of decitabine improved the efficacy of carrelizumab in relapsed and refractory cHL.
In addition to the above drugs, ADC drugs targeting CD25, chimeric antigen receptor (CAR)-T cell therapy targeting CD30, and bispecific antibodies targeting CD30 and CD16a have all obtained good research results in HL .
Looking forward to the announcement of more HL-related clinical research results in the future.
Yimaitong: What are your expectations for the future diagnosis and treatment of HL? What new directions do you think are worth further exploration in this field? Professor Qian Zhengzi currently has a good overall prognosis for cHL patients.
The emergence of new immunotherapy-related drugs improves the efficacy and reduces the side effects of HL patients.
Chemo-free (no chemotherapy regimen) will be the future development direction of HL treatment.
The goal is to allow more HL patients to obtain deep remission while reducing the toxic side effects of HL patients and improving the quality of life.
In addition, the prognostic model of HL is also a research direction worth exploring.
I look forward to the emergence of a better HL prognosis model in the future, which can identify cHL patients with poor prognosis as early as possible in the clinic, and carry out intensive treatment such as CAR-T cell therapy for these patients as soon as possible to improve the prognosis of these patients.
Poke "read the original text" and we will make progress together
In order to further improve the level of diagnosis and treatment of lymphoma in my country, the CSCO Anti-Lymphoma Alliance Tour-Tianjin Station Conference will be held on March 27, 2021.
This conference is based on the clinic, focusing on the frontier progress of lymphoma, and discussing the diagnosis and treatment of lymphoma in depth.
At this conference, Yimaitong was fortunate to interview Professor Qian Zhengzi from Tianjin Medical University Cancer Hospital to share the current status of diagnosis and treatment of Hodgkin’s Lymphoma (HL) and the latest progress.
Professor Qian Zhengzi, Associate Chief Physician, Doctor of Oncology CSCO Head and Neck Tumor Professional Committee Member, Tianjin Anti-Cancer Association Lymphoma Professional Committee Standing Committee Member of "Leukemia-Lymphoma" Journal Editor Yi Maitong: Could you please introduce me, Hodgkin What is the current status of diagnosis and treatment of lymphoma (HL)? Are there unmet clinical needs? Professor Qian Zhengzi The incidence of Hodgkin's Lymphoma (HL) in my country is relatively low, accounting for about 9% of all lymphoma subtypes, far below the level of 30% in European and American countries.
Most HL patients in my country are classical Hodgkin lymphoma (cHL), accounting for about 95%.
The prognosis of HL is relatively good, the 5-year survival rate is about 80%-90%, and most HL patients can achieve better survival after first-line treatment.
Relapsed and refractory cHL is currently mainly treated with salvage chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) for consolidation therapy, and the curative effect is relatively good.
However, there are still many unmet clinical needs for HL.
After the first-line ABVD chemotherapy of cHL patients, the 5-year failure-free survival (FFS) rate is only 70%, and 30% of patients will relapse and refractory.
Among them, 5%-9% of patients are primary refractory, and 10%-20% of patients will relapse.
As there is still a lack of mature and effective molecular markers, how to screen out these relapsed and refractory patients at the initial stage of treatment is a difficult problem for HL treatment.
A study explored the IHL30 model that included 18 genetic testing of the HL tumor microenvironment.
The results of the study showed that the FFS rate of patients with high scores under this model was only 41%, and the FFS rate of patients with low scores could reach 92%, but the two groups There was no significant difference in the overall survival (OS) of the patients.
Considering that genetic testing has not yet been widely carried out, the clinical application of this model is still facing some difficulties, and it is necessary to explore a more simplified HL prognosis model in clinical practice.
Another unmet need for treatment of HL is the efficacy of conventional second-line salvage treatment.
At present, the efficacy of conventional second-line chemotherapy for HL is limited, with a complete remission (CR) rate of about 20%-50%.
Very few patients can receive ASCT consolidation therapy.
At present, it is necessary to explore more new drugs to increase the CR rate of second-line salvage chemotherapy for HL patients, so that more HL patients can successfully bridge ASCT.
In addition, the trade-off between long-term efficacy and long-term survival of HL is also an unmet clinical need.
The current treatment of HL is based on chemotherapy, mainly using ABVD regimen, enhanced BEACOP regimen and other chemotherapy regimens.
Although intensive chemotherapy can bring better curative effects, it also brings toxic side effects such as reproductive toxicity, cardiotoxicity, pulmonary toxicity, and second primary tumors to HL patients.
Therefore, it is necessary to screen out HL patients with better prognosis in clinical practice, reduce the intensity and cycle of chemotherapy in these patients, and reduce toxic and side effects; at the same time, for patients with poor prognosis, they can be combined with other individualized treatments on the basis of intensive treatment to improve The patient's cure is possible.
At present, the adjustment of clinical treatment strategies for HL still depends on the guidance of mid-term PET-CT detection.
The AHL2011 study explored the adjustment of the HL treatment strategy guided by the PET-CT test.
The study of patients with advanced HL received 6 cycles of intensive BEACOP treatment, and PET-CT testing was performed after the second and fourth cycles of treatment.
PET- The follow-up treatment plan for patients with negative CT test was adjusted to ABVD plan.
The long-term follow-up results of the study showed that patients with negative PET-CT tests after the second and fourth cycles of treatment had better progression-free survival (PFS) and OS than those with positive PET-CT tests after the second and fourth cycles of treatment; 2.
The adjustment of treatment strategy after 4 cycles did not affect the survival of HL patients, and at the same time reduced the incidence of secondary primary tumors, infertility, thrombocytopenia ≥3 grade, and anemia in HL patients.
PET-CT detection is still an important guide for the adjustment of the current HL treatment plan.
Yimaitong: In recent years, great progress has been made in the field of lymphoma treatment.
Can you sum up and review for us, what new progress has been made in the field of classic HL diagnosis and treatment? Professor Qian Zhengzi has seen many new drugs in the field of HL treatment in recent years.
Whether it is an immunotherapeutic drug represented by antibody-conjugated drugs (ADC) verbutuximab (BV) and various PD-1 inhibitors, or targeted drugs represented by nalidomide and bendamustine Both have achieved good results.
At present, the application of BV in the treatment of HL is relatively mature and has been indicated for HL in many countries/regions.
The ECHELON-1 study compared the efficacy of BV combined with AVD regimen and ABVD regimen in newly treated advanced HL patients.
The long-term follow-up results showed that the 5-year PFS rate of the BV group was significantly better than that of the ABVD group (3-year PFS rate: 83.
1% vs 76.
0%; HR: 0.
70; P=0.
005).
The results of the study announced at the 2019 ASH Conference showed that the complete metabolic remission (CMR) rate of second-line patients with relapsed and refractory HL after receiving BV combined with ICE salvage chemotherapy can reach 69.
2%, which is a better bridge to ASCT.
In addition, BV can also be used for maintenance treatment of high-risk HL patients after ASCT to improve PFS.
For older HL patients who cannot tolerate chemotherapy, the treatment of the BV single-drug combination regimen can also improve the efficacy of the patient, reduce the side effects, and improve the quality of life of the patient.
PD-1 inhibitors are also relatively mature drugs in the treatment of HL, and have been included in the NCCN guidelines as a treatment recommendation for relapsed and refractory HL.
At present, the overall effective rate (ORR) of PD-1 inhibitors in the treatment of HL is about 60%-80%, but the CR rate is relatively low.
Among them, tislelizumab, which has been on the market in recent years, has an excellent effect on HL, with a CR rate of 61%.
The KEYNOTE-204 study compared the efficacy of PD-1 inhibitor pembrolizumab and BV in relapsed and refractory cHL.
The results of the study showed that the PFS of the pembrolizumab group was better than that of the BV group, reaching 13.
2 month.
Another study explored the efficacy of pembrolizumab combined with BVD regimen in relapsed and refractory cHL.
The results of the study showed that the CR rate of the combined regimen was as high as 95%, and the ORR reached 100%.
This joint solution can bring deep relief to cHL and is also suitable for bridging ASCT.
In addition to pembrolizumab, the PD-1 inhibitor nivolizumab also showed good efficacy in HL.
The Checkmate-205 study explored the efficacy of nivolumab combined with AVD in patients with advanced cHL.
The results of the study showed that the ORR of the program in cHL patients reached 86%, the CMR rate reached 75%, and the efficacy was considerable.
For patients who relapse after ASCT or who are not suitable for ASCT, it is recommended to receive PD-1 inhibitor treatment.
Related studies have also explored the advancement of PD-1 inhibitors in the treatment of HL.
A study released in 2020 explored the early stages of poor prognosis of the PD-1 inhibitor nivolumab combined with AVD regimen in simultaneous or sequential treatment.
The curative effect of cHL, the results of the study showed: the CR rate of this program reached 90%, and after a median follow-up of 2 years, the 2-year PFS rate of cHL patients reached 98%, and the 2-year OS rate reached 100%.
PD-1 inhibitors also have certain potential in the first-line treatment of HL.
The combination of BV and PD-1 inhibitors is also a research hotspot in the treatment of HL.
The Checkmate-744 study explored the efficacy of BV combined with nivolumab and bendamustine in patients with relapsed and refractory cHL aged 5-30 years.
The results of the study showed that the CMR of the combined program can reach 88%.
Well tolerated.
Another study explored the efficacy of BV combined with nivolumab in the maintenance treatment of high-risk HL patients after ASCT.
The results of the study showed that: 6 patients who did not reach CR after ASCT received BV combined with nivolumab, 5 cases The patients subsequently reached CR status, and the combined program significantly improved the PFS of HL patients.
Professor Han Weidong of my country explored the efficacy of PD-1 inhibitor carrelizumab combined with epigenetic drug decitabine in relapsed and refractory cHL.
The results of the study showed that the CR rate of the combined regimen reached 71%.
The addition of decitabine improved the efficacy of carrelizumab in relapsed and refractory cHL.
In addition to the above drugs, ADC drugs targeting CD25, chimeric antigen receptor (CAR)-T cell therapy targeting CD30, and bispecific antibodies targeting CD30 and CD16a have all obtained good research results in HL .
Looking forward to the announcement of more HL-related clinical research results in the future.
Yimaitong: What are your expectations for the future diagnosis and treatment of HL? What new directions do you think are worth further exploration in this field? Professor Qian Zhengzi currently has a good overall prognosis for cHL patients.
The emergence of new immunotherapy-related drugs improves the efficacy and reduces the side effects of HL patients.
Chemo-free (no chemotherapy regimen) will be the future development direction of HL treatment.
The goal is to allow more HL patients to obtain deep remission while reducing the toxic side effects of HL patients and improving the quality of life.
In addition, the prognostic model of HL is also a research direction worth exploring.
I look forward to the emergence of a better HL prognosis model in the future, which can identify cHL patients with poor prognosis as early as possible in the clinic, and carry out intensive treatment such as CAR-T cell therapy for these patients as soon as possible to improve the prognosis of these patients.
Poke "read the original text" and we will make progress together
