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On September 25-29, 2021, the 24th National Conference on Clinical Oncology and the 2021 CSCO Academic Annual Meeting will be held as scheduled
.
As one of the sub-venues of hematological tumors, "Lymphoma·Leukemia Special Session" gathered many experts and scholars in the field of lymphoma to bring rigorous scientific research discussions to the tumor industry and doctors with collective wisdom, and contribute to the joint promotion of the development of the tumor industry.
Force
.
Innovative targets empower the development of new drugs.
Roche's latest blood research and development products have made new breakthroughs in the treatment of diffuse large B-cell lymphoma.
In addition, they have also attracted attention in the treatment of indolent non-Hodgkin's lymphoma
.
For this reason, Yimaitong specially invited Professor Ma Jun from Harbin Institute of Hematology and Tumor and Professor Zhu Jun from Peking University Cancer Hospital to conduct in-depth analysis of relevant content
.
01 Diffuse large B-cell lymphoma (DLBCL) has always been the standard first-line program for DLBCL with R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone)
.
How to further improve the efficacy of combined chemotherapy on this basis, many attempts have been made in the past two decades: (1) Increase the intensity of chemotherapy; (2) Optimize anti-CD20 monoclonal antibody; (3) Carry out maintenance therapy and increase the dose of rituximab ; (4) Combine new drugs on the basis of the R-CHOP program
.
However, none of the above attempts surpassed the efficacy of R-CHOP and failed to improve the long-term survival of patients
.
It was not until the advent of the anti-CD79b antibody drug conjugate (ADC) Polatuzumab vedotin (Pola) that this situation was broken
.
01Pola combined with CHP is expected to break through the “ceiling” of R-CHOP first-line treatment.
The recently announced global multi-center Phase III Polarix study included 879 newly-treated DLBCL patients who received 6 cycles of Pola combined with R-CHP (rituximab, ring Phosphoramide, doxorubicin, prednisone) treatment, or 6 cycles of R-CHOP regimen treatment group, followed by 2 cycles of rituximab treatment
.
Studies have shown that Pola combined with R-CHP can significantly prolong the progression-free survival (PFS) of newly treated DLBCL patients and has clinical significance.
The study has reached the primary endpoint, and the safety results are consistent with previously observed results
.
The study confirmed that the treatment of Pola combined with R-CHP is the first to extend the progression-free survival of DLBCL compared with standard treatment in 20 years
.
The 02 Pola+BR regimen brings new hope to patients with relapsed and refractory (R/R) DLBCL.
The Pola+BR (bendamustine, rituximab) regimen was approved by the FDA in 2019 to treat R/R DLBCL patients
.
In a randomized phase II study published in J Clin Oncol in 2020, the remission rate of the Pola+BR regimen for non-transplantable R/R DLBCL was significantly higher than that of the BR group (optimal overall remission rate 70% vs.
33%, complete remission The rate was 58% vs.
20%), the median PFS (9.
5 vs 3.
7 months) and median OS (12.
4 vs 4.
7 months) were also longer than those in the BR group, and treatment-related toxicity was controllable
.
In addition, a multi-center real-world study in the United Kingdom has confirmed that for R/R DLBCL, the Pola combined BR regimen has shown better clinical benefits in terms of treatment.
The overall response rate (ORR) of the whole group is 57.
0%, which is very good.
Clinical application prospects
.
Figure 1 The British real-world study: Pola combined with BR in the treatment of R/R DLBCL is based on the principle that Pola and lenalidomide have different drug action mechanisms, and the adverse reactions of the two do not overlap.
The researchers tried Pola+rituximab+ A combination of lenalidomide (Pola-R-Len) three-drug combination regimen, a phase Ib/II study evaluated the efficacy of Pola-R-Len in R/R DLBCL.
The CR rate at the end of the treatment was 29%.
Among the patients who achieved CR, most patients were still in continuous remission; the median PFS was 6.
3 months, and the median OS was 10.
9 months
.
Figure 2 Pola-R-Len treatment of R/R DLBCL patients with remission rate and median duration of remission (DOR), PFS and OS03 bispecific antibodies shine in the field of DLBCL Glofitamab (Glofit) and Mosunetuzumab (Mosun) are targets Bispecific antibodies to CD20/CD3 are based on Roche’s unique bi-antibody technology development platform.
These two antibodies are ready to be developed in the lymphoma field
.
Glofit has 2 CD20 binding sites and 1 CD3 binding site (ie "2:1" double antibody).
The "2:1" double antibody has a higher activity than the traditional "1:1" double antibody.
1000 times, has stronger target binding ability and effect, can play a stronger tumor cell killing and lysis effect with lower antibody concentration
.
At present, Glofitamab has launched a number of clinical trials at home and abroad, which is expected to bring new treatment options to patients with R/R DLBCL treated with ≥2 line system
.
Among the elderly/intolerant conventional immunochemotherapy patients, the early results of Mosun single-agent first-line treatment have shown sustained efficacy and good safety, and it is expected to become the first drug of its kind to be marketed abroad
.
02 Indolent non-Hodgkin's lymphoma (iNHL) iNHL is a type of lymphoma with relatively slow clinical progression, but it is difficult to cure and prone to repeated recurrence
.
Although the emergence of rituximab has broken this treatment dilemma, in order to determine the treatment plan that maximizes the benefit of patients, the exploration of treatment in the field of laziness has never stopped
.
01Otuzumab opens a new chapter in lazy lymph therapy.
Otuzumab combined with chemotherapy is the world's first regimen that surpasses rituximab combined with chemotherapy in the first-line treatment of follicular lymphoma (FL).
It has been awarded in China Batch treatment of initial FL induction and maintenance treatment
.
Otuzumab has been approved for multiple indications for lazy leaching in foreign countries, opening a new era of lazy leaching new anti-CD20 monoclonal antibody therapy
.
The results of the GALLIUM study showed that compared with R-chemotherapy, otuzumab combined with chemotherapy reduced the risk of progression, recurrence and death in FL patients by 34%, and the relative risk of POD24 events was reduced by 46%
.
In addition, the rapid infusion of otuzumab is safe and well tolerated.
Since the second cycle, the safety of otuzumab infusion (SDI) for 90 minutes has not been found in FL patients.
No new safety signals have been found.
, Has been verified in GAZELLE research
.
The final analysis result of the GADOLIN study indicated that the combination of otuzumab and bendamustine (GB) regimen in iNHL patients can reduce the risk of disease progression or death by 43% compared with B monotherapy, and it has a continuous and clinically significant effect on patients.
OS benefits
.
Sequential otuzumab maintenance therapy after GB regimen induction therapy may become the new standard therapy
.
In addition to FL, otuzumab has also carried out related studies in other iNHLs to evaluate the efficacy and safety
.
Update on the results of the 4-year follow-up of the CLL14 study: Compared with the combination of otuzumab combined with chlorambucil, and the fixed course of otuzumab combined with Venecla, patients with different risk types (including patients with TP53 mutation/deletion, IGHV not Patients with mutations) showed sustained PFS benefit (mPFS NR vs.
36.
4 months)
.
02 Lazilin’s “No Chemotherapy” program can be expected in the future In order to improve survival and tolerance, iNHL’s treatment mode has gradually focused on targeted and immune drugs.
The era of “no chemotherapy” is just around the corner, and many treatment options are also in full swing.
Development
.
The LYSA Phase II study evaluated the efficacy of otuzumab + atezolizumab + venacral (G-Atezo-Ven) regimen in R/R iNHL.
The study showed that the FL cohort had a median follow-up of 14.
5 months, ORR The marginal zone lymphoma (MZL) cohort had a median follow-up of 11.
9 months, with an ORR of 66.
76%.
Both the MZL and FL cohorts achieved durable remission.
Only 21.
4% of the responders reported recurrence/progress, and no unexpected results Toxicity
.
The efficacy of otuzumab combined with lenalidomide (Glen) in newly-treated and R/R FL patients is also worthy of attention
.
The results of the study announced at the ASCO conference in 2020 showed that at a median follow-up of 25 months, Glen's ORR for newly treated FL reached 96%, and the CR rate reached 94%
.
A phase II result showed that the ORR of Glen's treatment of R/R FL reached 100%, and the CR rate reached 75%
.
The results of Pola combined with Otuzumab and Pola-G-Ven (Pola-G-Ven) in R/R FL patients announced at the ASCO annual meeting this year
.
The safety of the triple regimen is consistent with single-agent toxicity.
After a median follow-up of 14.
4 months, the 12-month PFS rate was 73%, and mPFS has not yet reached
.
The innovative use of chemotherapy-free regimens is expected to bring hope for treatment to more patients
.
In addition, the efficacy of the CD20/CD3 anti-Mosun in the R/R FL population is worth looking forward to
.
The GO29781 study showed that the ORR of R/R FL patients who had received ≥2 line systemic treatment with Mosun monotherapy was 67.
7%, the CR rate was 51.
6%, and the DOR was 20.
4 months, which can achieve a high sustained remission.
At the same time, the investigator also In exploring the efficacy of different combination schemes, it is hoped that more patients can be benefited as soon as possible
.
Big coffee commented on Professor Ma Jun.
In the past 20 years, the diagnosis and treatment of lymphoma in China has made rapid progress, and targeted therapies have sprung up
.
In June 2021, otuzumab was approved in China, bringing new dawn to Chinese patients
.
As a new humanized anti-CD20 monoclonal antibody, its antibody-dependent cytotoxicity (ADCC) has been significantly enhanced
.
In addition to the field of indolent lymphoma, otuzumab-based therapies have now "full bloom" in the field of lymphoma treatment.
In addition to FL indications, the FDA has approved otuzumab combined with ibrutinib and veneclair For the initial treatment of patients with chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL), its exploration in mantle cell lymphoma (MCL) and other B-cell lymphomas has also been deployed, and the prospects are worth looking forward to
.
Professor Zhu Jun DLBCL patients will face relapse after receiving initial treatment, about 40%~50%, the treatment options available at this time are very limited, so continuing to explore R-CHOP in the first-line treatment can further improve the patient’s cure and survival The new program has important clinical significance
.
Based on the results of a randomized phase II study, the ready-to-use fixed-course treatment plan of Pola combined with BR for the treatment of R/R DLBCL has been approved in more than 60 countries/regions (including the European Union and the United States)
.
The recently announced global key phase III clinical study Polarix shows that the combination of Pola and R-CHP is the first treatment plan that can significantly improve patient outcomes compared with the standard treatment plan R-CHOP in the past 20 years.
It is expected to become a treatment for first-line DLBCL patients New choice
.
It is also gratifying that China has participated in the Polarix trial together and is also the main participant in the Asian subgroup.
I look forward to the detailed research results that will be announced on ASH this year.
I hope that Pola will be approved for listing in China as soon as possible, bringing it to Chinese DLBCL patients.
More hope of healing
.
Summary The theme of this year's CSCO annual meeting is "Focus on innovative research and lead the original future"
.
It is self-evident that the research and development of innovative drugs will prolong the life cycle of patients and improve the comfort of life.
We hope that these new tumor drugs will be approved for marketing in China as soon as possible, increase treatment options, and help achieve the grand goal of "Healthy China 2030"
.
Poke "read the original text", we make progress together
.
As one of the sub-venues of hematological tumors, "Lymphoma·Leukemia Special Session" gathered many experts and scholars in the field of lymphoma to bring rigorous scientific research discussions to the tumor industry and doctors with collective wisdom, and contribute to the joint promotion of the development of the tumor industry.
Force
.
Innovative targets empower the development of new drugs.
Roche's latest blood research and development products have made new breakthroughs in the treatment of diffuse large B-cell lymphoma.
In addition, they have also attracted attention in the treatment of indolent non-Hodgkin's lymphoma
.
For this reason, Yimaitong specially invited Professor Ma Jun from Harbin Institute of Hematology and Tumor and Professor Zhu Jun from Peking University Cancer Hospital to conduct in-depth analysis of relevant content
.
01 Diffuse large B-cell lymphoma (DLBCL) has always been the standard first-line program for DLBCL with R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone)
.
How to further improve the efficacy of combined chemotherapy on this basis, many attempts have been made in the past two decades: (1) Increase the intensity of chemotherapy; (2) Optimize anti-CD20 monoclonal antibody; (3) Carry out maintenance therapy and increase the dose of rituximab ; (4) Combine new drugs on the basis of the R-CHOP program
.
However, none of the above attempts surpassed the efficacy of R-CHOP and failed to improve the long-term survival of patients
.
It was not until the advent of the anti-CD79b antibody drug conjugate (ADC) Polatuzumab vedotin (Pola) that this situation was broken
.
01Pola combined with CHP is expected to break through the “ceiling” of R-CHOP first-line treatment.
The recently announced global multi-center Phase III Polarix study included 879 newly-treated DLBCL patients who received 6 cycles of Pola combined with R-CHP (rituximab, ring Phosphoramide, doxorubicin, prednisone) treatment, or 6 cycles of R-CHOP regimen treatment group, followed by 2 cycles of rituximab treatment
.
Studies have shown that Pola combined with R-CHP can significantly prolong the progression-free survival (PFS) of newly treated DLBCL patients and has clinical significance.
The study has reached the primary endpoint, and the safety results are consistent with previously observed results
.
The study confirmed that the treatment of Pola combined with R-CHP is the first to extend the progression-free survival of DLBCL compared with standard treatment in 20 years
.
The 02 Pola+BR regimen brings new hope to patients with relapsed and refractory (R/R) DLBCL.
The Pola+BR (bendamustine, rituximab) regimen was approved by the FDA in 2019 to treat R/R DLBCL patients
.
In a randomized phase II study published in J Clin Oncol in 2020, the remission rate of the Pola+BR regimen for non-transplantable R/R DLBCL was significantly higher than that of the BR group (optimal overall remission rate 70% vs.
33%, complete remission The rate was 58% vs.
20%), the median PFS (9.
5 vs 3.
7 months) and median OS (12.
4 vs 4.
7 months) were also longer than those in the BR group, and treatment-related toxicity was controllable
.
In addition, a multi-center real-world study in the United Kingdom has confirmed that for R/R DLBCL, the Pola combined BR regimen has shown better clinical benefits in terms of treatment.
The overall response rate (ORR) of the whole group is 57.
0%, which is very good.
Clinical application prospects
.
Figure 1 The British real-world study: Pola combined with BR in the treatment of R/R DLBCL is based on the principle that Pola and lenalidomide have different drug action mechanisms, and the adverse reactions of the two do not overlap.
The researchers tried Pola+rituximab+ A combination of lenalidomide (Pola-R-Len) three-drug combination regimen, a phase Ib/II study evaluated the efficacy of Pola-R-Len in R/R DLBCL.
The CR rate at the end of the treatment was 29%.
Among the patients who achieved CR, most patients were still in continuous remission; the median PFS was 6.
3 months, and the median OS was 10.
9 months
.
Figure 2 Pola-R-Len treatment of R/R DLBCL patients with remission rate and median duration of remission (DOR), PFS and OS03 bispecific antibodies shine in the field of DLBCL Glofitamab (Glofit) and Mosunetuzumab (Mosun) are targets Bispecific antibodies to CD20/CD3 are based on Roche’s unique bi-antibody technology development platform.
These two antibodies are ready to be developed in the lymphoma field
.
Glofit has 2 CD20 binding sites and 1 CD3 binding site (ie "2:1" double antibody).
The "2:1" double antibody has a higher activity than the traditional "1:1" double antibody.
1000 times, has stronger target binding ability and effect, can play a stronger tumor cell killing and lysis effect with lower antibody concentration
.
At present, Glofitamab has launched a number of clinical trials at home and abroad, which is expected to bring new treatment options to patients with R/R DLBCL treated with ≥2 line system
.
Among the elderly/intolerant conventional immunochemotherapy patients, the early results of Mosun single-agent first-line treatment have shown sustained efficacy and good safety, and it is expected to become the first drug of its kind to be marketed abroad
.
02 Indolent non-Hodgkin's lymphoma (iNHL) iNHL is a type of lymphoma with relatively slow clinical progression, but it is difficult to cure and prone to repeated recurrence
.
Although the emergence of rituximab has broken this treatment dilemma, in order to determine the treatment plan that maximizes the benefit of patients, the exploration of treatment in the field of laziness has never stopped
.
01Otuzumab opens a new chapter in lazy lymph therapy.
Otuzumab combined with chemotherapy is the world's first regimen that surpasses rituximab combined with chemotherapy in the first-line treatment of follicular lymphoma (FL).
It has been awarded in China Batch treatment of initial FL induction and maintenance treatment
.
Otuzumab has been approved for multiple indications for lazy leaching in foreign countries, opening a new era of lazy leaching new anti-CD20 monoclonal antibody therapy
.
The results of the GALLIUM study showed that compared with R-chemotherapy, otuzumab combined with chemotherapy reduced the risk of progression, recurrence and death in FL patients by 34%, and the relative risk of POD24 events was reduced by 46%
.
In addition, the rapid infusion of otuzumab is safe and well tolerated.
Since the second cycle, the safety of otuzumab infusion (SDI) for 90 minutes has not been found in FL patients.
No new safety signals have been found.
, Has been verified in GAZELLE research
.
The final analysis result of the GADOLIN study indicated that the combination of otuzumab and bendamustine (GB) regimen in iNHL patients can reduce the risk of disease progression or death by 43% compared with B monotherapy, and it has a continuous and clinically significant effect on patients.
OS benefits
.
Sequential otuzumab maintenance therapy after GB regimen induction therapy may become the new standard therapy
.
In addition to FL, otuzumab has also carried out related studies in other iNHLs to evaluate the efficacy and safety
.
Update on the results of the 4-year follow-up of the CLL14 study: Compared with the combination of otuzumab combined with chlorambucil, and the fixed course of otuzumab combined with Venecla, patients with different risk types (including patients with TP53 mutation/deletion, IGHV not Patients with mutations) showed sustained PFS benefit (mPFS NR vs.
36.
4 months)
.
02 Lazilin’s “No Chemotherapy” program can be expected in the future In order to improve survival and tolerance, iNHL’s treatment mode has gradually focused on targeted and immune drugs.
The era of “no chemotherapy” is just around the corner, and many treatment options are also in full swing.
Development
.
The LYSA Phase II study evaluated the efficacy of otuzumab + atezolizumab + venacral (G-Atezo-Ven) regimen in R/R iNHL.
The study showed that the FL cohort had a median follow-up of 14.
5 months, ORR The marginal zone lymphoma (MZL) cohort had a median follow-up of 11.
9 months, with an ORR of 66.
76%.
Both the MZL and FL cohorts achieved durable remission.
Only 21.
4% of the responders reported recurrence/progress, and no unexpected results Toxicity
.
The efficacy of otuzumab combined with lenalidomide (Glen) in newly-treated and R/R FL patients is also worthy of attention
.
The results of the study announced at the ASCO conference in 2020 showed that at a median follow-up of 25 months, Glen's ORR for newly treated FL reached 96%, and the CR rate reached 94%
.
A phase II result showed that the ORR of Glen's treatment of R/R FL reached 100%, and the CR rate reached 75%
.
The results of Pola combined with Otuzumab and Pola-G-Ven (Pola-G-Ven) in R/R FL patients announced at the ASCO annual meeting this year
.
The safety of the triple regimen is consistent with single-agent toxicity.
After a median follow-up of 14.
4 months, the 12-month PFS rate was 73%, and mPFS has not yet reached
.
The innovative use of chemotherapy-free regimens is expected to bring hope for treatment to more patients
.
In addition, the efficacy of the CD20/CD3 anti-Mosun in the R/R FL population is worth looking forward to
.
The GO29781 study showed that the ORR of R/R FL patients who had received ≥2 line systemic treatment with Mosun monotherapy was 67.
7%, the CR rate was 51.
6%, and the DOR was 20.
4 months, which can achieve a high sustained remission.
At the same time, the investigator also In exploring the efficacy of different combination schemes, it is hoped that more patients can be benefited as soon as possible
.
Big coffee commented on Professor Ma Jun.
In the past 20 years, the diagnosis and treatment of lymphoma in China has made rapid progress, and targeted therapies have sprung up
.
In June 2021, otuzumab was approved in China, bringing new dawn to Chinese patients
.
As a new humanized anti-CD20 monoclonal antibody, its antibody-dependent cytotoxicity (ADCC) has been significantly enhanced
.
In addition to the field of indolent lymphoma, otuzumab-based therapies have now "full bloom" in the field of lymphoma treatment.
In addition to FL indications, the FDA has approved otuzumab combined with ibrutinib and veneclair For the initial treatment of patients with chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL), its exploration in mantle cell lymphoma (MCL) and other B-cell lymphomas has also been deployed, and the prospects are worth looking forward to
.
Professor Zhu Jun DLBCL patients will face relapse after receiving initial treatment, about 40%~50%, the treatment options available at this time are very limited, so continuing to explore R-CHOP in the first-line treatment can further improve the patient’s cure and survival The new program has important clinical significance
.
Based on the results of a randomized phase II study, the ready-to-use fixed-course treatment plan of Pola combined with BR for the treatment of R/R DLBCL has been approved in more than 60 countries/regions (including the European Union and the United States)
.
The recently announced global key phase III clinical study Polarix shows that the combination of Pola and R-CHP is the first treatment plan that can significantly improve patient outcomes compared with the standard treatment plan R-CHOP in the past 20 years.
It is expected to become a treatment for first-line DLBCL patients New choice
.
It is also gratifying that China has participated in the Polarix trial together and is also the main participant in the Asian subgroup.
I look forward to the detailed research results that will be announced on ASH this year.
I hope that Pola will be approved for listing in China as soon as possible, bringing it to Chinese DLBCL patients.
More hope of healing
.
Summary The theme of this year's CSCO annual meeting is "Focus on innovative research and lead the original future"
.
It is self-evident that the research and development of innovative drugs will prolong the life cycle of patients and improve the comfort of life.
We hope that these new tumor drugs will be approved for marketing in China as soon as possible, increase treatment options, and help achieve the grand goal of "Healthy China 2030"
.
Poke "read the original text", we make progress together
