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From March 20 to March 21, 2021, the 4th Chinese Lymphoma Individualized Treatment Conference and the 2021 Chinese Anti-Cancer Association Lymphoma jointly sponsored by the Lymphoma Professional Committee of the Chinese Anti-Cancer Association and the Oncologist Branch of the Chinese Medical Doctor Association The annual meeting of the professional committee has been successfully held in Beijing.
At this conference, Professor Zhang Huilai from the Cancer Hospital of Tianjin Medical University shared "New progress in the treatment of peripheral T-cell lymphoma (PTCL) led by new drugs", and shared the following for readers.
PTCL disease overview and molecular typing progress PTCL is a group of highly heterogeneous diseases derived from mature T cells and NK cells.
In China, PTCL accounts for about 20% of non-Hodgkin's lymphoma (NHL), which is much lower than B-cell lymphoma.
According to the latest version of the WHO classification, there are more than 25 subtypes of PTCL, and the distribution area of each subtype is quite different.
Past analysis data shows that the top 3 NHL-T subtypes in China are extranodal NK/T cell lymphoma, PTCL-non-specific (PTCL-NOS) and ALK+ anaplastic large cell lymphoma (ALK+ ALCL).
Figure 1 The low incidence and heterogeneity of the distribution of NHL-T subtypes in China hinder the development of PTCL treatment, and the prognosis of patients is generally poor (5-year survival rate is less than 30%).
After years of research, traditional CHOP chemotherapy and improved programs are not satisfactory.
Therefore, new therapies and methods are urgently needed to improve the survival outcome of patients.
In recent years, the research on molecular typing of PTCL has been intensified.
A document published on Blood in 2014 incorporated gene expression profile (GEP) into the PTCL classification, and divided PTCL-NOS into GATA3 (related to PI3K and mTOR pathways), TBX21 (related to NFκB and STAT3 pathways) and Unclassifiable Three types.
A paper published on Blood in 2019 included 4 indicators, including GATA3, CCR4, TBX21, CXCR3, according to the expression of immunohistochemistry (IHC), and also divided PTCL into different types.
Analysis shows that GEP classification is basically consistent with IHC classification, and there is no significant difference in prognostic stratification (Figure 2-3).
Figure 2 Comparison between GEP classification and IHC classification Figure 3 Comparison of prognosis between GEP classification and IHC classification Vebutuximab combined with chemotherapy has become a new choice for the first-line treatment of PTCL patients ECHELON-2 study is a randomized, double-blind A, placebo-controlled international phase III clinical study included 452 newly-treated adult PTCL patients with CD30 expression ≥10%, and were treated with verbutuximab combined with cyclophosphamide, doxorubicin, and prednisone.
The chemotherapy regimen (A+CHP group) and the four-drug combination therapy regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP group) are planned to observe its efficacy and safety.
The results showed that the median PFS of the A+CHP group was 48.
2 months, and the 3-year PFS was 57%, which was significantly better than that of the CHOP group (Figure 4); in addition, A+CHP reduced the risk of death in PTCL patients by 34% (Figure 4).
5).
Figure 4 Comparison of PFS between the two groups Figure 5 Analysis of OS between the two groups showed that in almost all subgroups, the treatment benefit of the A+CHP group was better than that of the CHOP group (Figure 6).
In terms of safety, the incidence and severity of adverse events ≥20% in the two groups were similar (Figure 7).
Figure 6 Comparison of different subgroups Figure 7 Analysis of safety situation The results of this study confirmed that the first-line treatment of Verbutuximab combined with chemotherapy (BV+CHP) can significantly increase the PFS and OS of CD30-positive PTCL patients, and significantly change the treatment of PTCL Pattern and patient survival pattern.
Therefore, the BV+CHP program has been recommended by the 2020NCCN guidelines as the first-line treatment program for PTCL patients.
Figure 8 NCCN Guidelines (2020) cut-off Professor Zhang said that the patients included in the study are all CD30-positive patients.
In the future, we will further explore the relationship between CD30 expression and treatment response, the best cut-off point of CD30-positive, and other mechanisms of action of BV, etc.
, May have a profound impact on the use of drugs in more PTCL subtypes and patients.
Will PTCL patients be transplanted after the first-line treatment is relieved? Choose autologous transplantation or allogeneic transplantation? Professor Zhang pointed out that for ALK+ ALCL high-risk International Prognostic Index (IPI) patients and other types of conditional patients, they can receive high-dose chemotherapy combined with auto-SCT for consolidation after first-line treatment remission, but there is currently no prospective The sample size study confirms this conclusion; for some patients with PTCL with very poor prognosis (such as liver and spleen T-cell lymphoma), first-line allogeneic hematopoietic stem cell transplantation (allo-SCT) can be selected to consolidate, but there is also a lack of large sample size research.
data support.
Then, Professor Zhang also introduced to us two clinical studies on transplantation of PTCL patients reported in the Lugano Conference in 2019.
Among them, one is a multi-center, retrospective clinical study (GELTAMO/FIL study) to evaluate the impact of transplantation on PFS and OS in PTCL patients.
The study included a total of 212 patients who obtained CR or CRu after first-line treatment.
The results showed that receiving ASCT after the first treatment reached CR can improve the survival rate of PTCL patients except ALK+ALCL.
(The 5-year PFS was 65% vs 44%, p=0.
012; OS was 74% vs 65%, p=0.
046) Figure 9 Analysis of the results of the GELTAMO/FIL study Another prospective randomized clinical trial (AATT study). The study compared the survival difference between alloSCT and autoSCT consolidation treatment in PTCL patients.
The median follow-up time was 42 months.
The results showed that there was no significant difference in survival between the two (EFS 43% vs 38%, p=0.
58; OS 57% vs 70%, p=0.
41), but alloSCT treatment will cause higher treatment-related deaths (TRM).
This also reminds us that for younger patients with PTCL, autoSCT is still the first choice for consolidation therapy, but for patients who relapse after autoSCT, alloSCT can be successfully rescued.
Figure 10 Analysis and outlook of AATT research results Finally, Professor Zhang concluded that the current treatment of first-line consolidation therapy and relapsed/refractory patients with PTCL is still being explored.
Various new chemotherapeutic drugs and new targeted drugs such as BV, Chidamide, PD-1, PD-L1 antibody, etc.
, provide new options for the treatment of PTCL.
Combination therapy of new drugs with different combinations will become the main research trend.
One.
In the future, the treatment model of PTCL may also be rewritten.
Professor Zhang Huilai Doctor of Oncology, Chief Physician, Doctoral Supervisor, Director of Lymphoma Medicine, Tianjin Medical University Cancer Hospital, Deputy Chairman, Lymphoma Professional Committee, Chinese Anti-Cancer Association, Member of the Standing Committee of the Chinese Society of Clinical Oncology (CSCO) Anti-Lymphoma Alliance, China Healthcare International Vice Chairman of the Oncology Branch of the Exchange Promotion Association Vice Chairman of the Lymphoma Professional Committee of the Chinese Geriatric Healthcare Association Member of the Standing Committee of the Chinese Society of Clinical Oncology (CSCO) Oncology and Cardiology Committee Member of the Lymphoma Group of the Oncology Branch of the Chinese Medical Association Tianjin Anti-Cancer Association Director of the Lymphoma Professional Committee Deputy Director of Tianjin Hematology Quality Control Center Deputy Director of Tianjin Medical Association Hematologist Branch Vice President Stamp "Read the original text", we make progress together
At this conference, Professor Zhang Huilai from the Cancer Hospital of Tianjin Medical University shared "New progress in the treatment of peripheral T-cell lymphoma (PTCL) led by new drugs", and shared the following for readers.
PTCL disease overview and molecular typing progress PTCL is a group of highly heterogeneous diseases derived from mature T cells and NK cells.
In China, PTCL accounts for about 20% of non-Hodgkin's lymphoma (NHL), which is much lower than B-cell lymphoma.
According to the latest version of the WHO classification, there are more than 25 subtypes of PTCL, and the distribution area of each subtype is quite different.
Past analysis data shows that the top 3 NHL-T subtypes in China are extranodal NK/T cell lymphoma, PTCL-non-specific (PTCL-NOS) and ALK+ anaplastic large cell lymphoma (ALK+ ALCL).
Figure 1 The low incidence and heterogeneity of the distribution of NHL-T subtypes in China hinder the development of PTCL treatment, and the prognosis of patients is generally poor (5-year survival rate is less than 30%).
After years of research, traditional CHOP chemotherapy and improved programs are not satisfactory.
Therefore, new therapies and methods are urgently needed to improve the survival outcome of patients.
In recent years, the research on molecular typing of PTCL has been intensified.
A document published on Blood in 2014 incorporated gene expression profile (GEP) into the PTCL classification, and divided PTCL-NOS into GATA3 (related to PI3K and mTOR pathways), TBX21 (related to NFκB and STAT3 pathways) and Unclassifiable Three types.
A paper published on Blood in 2019 included 4 indicators, including GATA3, CCR4, TBX21, CXCR3, according to the expression of immunohistochemistry (IHC), and also divided PTCL into different types.
Analysis shows that GEP classification is basically consistent with IHC classification, and there is no significant difference in prognostic stratification (Figure 2-3).
Figure 2 Comparison between GEP classification and IHC classification Figure 3 Comparison of prognosis between GEP classification and IHC classification Vebutuximab combined with chemotherapy has become a new choice for the first-line treatment of PTCL patients ECHELON-2 study is a randomized, double-blind A, placebo-controlled international phase III clinical study included 452 newly-treated adult PTCL patients with CD30 expression ≥10%, and were treated with verbutuximab combined with cyclophosphamide, doxorubicin, and prednisone.
The chemotherapy regimen (A+CHP group) and the four-drug combination therapy regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP group) are planned to observe its efficacy and safety.
The results showed that the median PFS of the A+CHP group was 48.
2 months, and the 3-year PFS was 57%, which was significantly better than that of the CHOP group (Figure 4); in addition, A+CHP reduced the risk of death in PTCL patients by 34% (Figure 4).
5).
Figure 4 Comparison of PFS between the two groups Figure 5 Analysis of OS between the two groups showed that in almost all subgroups, the treatment benefit of the A+CHP group was better than that of the CHOP group (Figure 6).
In terms of safety, the incidence and severity of adverse events ≥20% in the two groups were similar (Figure 7).
Figure 6 Comparison of different subgroups Figure 7 Analysis of safety situation The results of this study confirmed that the first-line treatment of Verbutuximab combined with chemotherapy (BV+CHP) can significantly increase the PFS and OS of CD30-positive PTCL patients, and significantly change the treatment of PTCL Pattern and patient survival pattern.
Therefore, the BV+CHP program has been recommended by the 2020NCCN guidelines as the first-line treatment program for PTCL patients.
Figure 8 NCCN Guidelines (2020) cut-off Professor Zhang said that the patients included in the study are all CD30-positive patients.
In the future, we will further explore the relationship between CD30 expression and treatment response, the best cut-off point of CD30-positive, and other mechanisms of action of BV, etc.
, May have a profound impact on the use of drugs in more PTCL subtypes and patients.
Will PTCL patients be transplanted after the first-line treatment is relieved? Choose autologous transplantation or allogeneic transplantation? Professor Zhang pointed out that for ALK+ ALCL high-risk International Prognostic Index (IPI) patients and other types of conditional patients, they can receive high-dose chemotherapy combined with auto-SCT for consolidation after first-line treatment remission, but there is currently no prospective The sample size study confirms this conclusion; for some patients with PTCL with very poor prognosis (such as liver and spleen T-cell lymphoma), first-line allogeneic hematopoietic stem cell transplantation (allo-SCT) can be selected to consolidate, but there is also a lack of large sample size research.
data support.
Then, Professor Zhang also introduced to us two clinical studies on transplantation of PTCL patients reported in the Lugano Conference in 2019.
Among them, one is a multi-center, retrospective clinical study (GELTAMO/FIL study) to evaluate the impact of transplantation on PFS and OS in PTCL patients.
The study included a total of 212 patients who obtained CR or CRu after first-line treatment.
The results showed that receiving ASCT after the first treatment reached CR can improve the survival rate of PTCL patients except ALK+ALCL.
(The 5-year PFS was 65% vs 44%, p=0.
012; OS was 74% vs 65%, p=0.
046) Figure 9 Analysis of the results of the GELTAMO/FIL study Another prospective randomized clinical trial (AATT study). The study compared the survival difference between alloSCT and autoSCT consolidation treatment in PTCL patients.
The median follow-up time was 42 months.
The results showed that there was no significant difference in survival between the two (EFS 43% vs 38%, p=0.
58; OS 57% vs 70%, p=0.
41), but alloSCT treatment will cause higher treatment-related deaths (TRM).
This also reminds us that for younger patients with PTCL, autoSCT is still the first choice for consolidation therapy, but for patients who relapse after autoSCT, alloSCT can be successfully rescued.
Figure 10 Analysis and outlook of AATT research results Finally, Professor Zhang concluded that the current treatment of first-line consolidation therapy and relapsed/refractory patients with PTCL is still being explored.
Various new chemotherapeutic drugs and new targeted drugs such as BV, Chidamide, PD-1, PD-L1 antibody, etc.
, provide new options for the treatment of PTCL.
Combination therapy of new drugs with different combinations will become the main research trend.
One.
In the future, the treatment model of PTCL may also be rewritten.
Professor Zhang Huilai Doctor of Oncology, Chief Physician, Doctoral Supervisor, Director of Lymphoma Medicine, Tianjin Medical University Cancer Hospital, Deputy Chairman, Lymphoma Professional Committee, Chinese Anti-Cancer Association, Member of the Standing Committee of the Chinese Society of Clinical Oncology (CSCO) Anti-Lymphoma Alliance, China Healthcare International Vice Chairman of the Oncology Branch of the Exchange Promotion Association Vice Chairman of the Lymphoma Professional Committee of the Chinese Geriatric Healthcare Association Member of the Standing Committee of the Chinese Society of Clinical Oncology (CSCO) Oncology and Cardiology Committee Member of the Lymphoma Group of the Oncology Branch of the Chinese Medical Association Tianjin Anti-Cancer Association Director of the Lymphoma Professional Committee Deputy Director of Tianjin Hematology Quality Control Center Deputy Director of Tianjin Medical Association Hematologist Branch Vice President Stamp "Read the original text", we make progress together
