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Foreword On December 10-11, 2021, the "2021 Cross-Strait Hematology Academic Conference" hosted by the Hematology Committee of the Cross-Strait Medical and Health Exchange Association will be held online.
This conference focuses on research in the field of hematology.
"New progress, new theory, new technology", the latest achievements and experience from basic to clinical, from frontier to practice, strive to comprehensively improve the understanding, screening, diagnosis and treatment of hematology and related diseases of grassroots medical workers
.
At the meeting, Professor Zhang Liling from the Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology gave a report on the topic of "New Progress in Peripheral T-Cell Lymphoma Targeted Therapy and Practice Sharing", respectively, in "Peripheral T-Cell Lymphoma (PTCL) Treatment" In-depth discussion will be carried out in three aspects, “Current situation”, “Optimization of initial treatment plan”, and “Exploration of relapse and refractory treatment plan”
.
This article organizes its main content as follows for the reference of readers
.
Current status of PTCL treatment 1.
The CHOP regimen is still the most common treatment regimen for PTCL.
Currently, the most common clinical treatment regimen for PTCL is still based on CHOP and CHOP-like chemotherapy
.
In Asian countries, CHOP and CHOEP are still the more commonly used regimens for the treatment of PTCL patients, and asparaginase-containing chemotherapy regimens are the mainstay for NK/T-cell lymphoma patients
.
2.
The prognosis of the previous CHOP regimen in first-line treatment is poor, and new treatment options need to be explored.
Professor Zhang said that the prognosis of PTCL patients is poor.
The low incidence and high heterogeneity make treatment progress relatively slow.
At present, most PTCL patients still accept The CHOP or CHOP-like treatment program has a lower complete remission (CR) rate, and poor progression-free survival (PFS) and overall survival (OS)
.
Except for ALK+ALCL, which has a lower IPI score, the 5-year OS rate of other patients is less than 50%, and patients with an IPI score> 2 have a worse prognosis
.
The proportion of relapsed and refractory patients is relatively high, and the long-term survival rate in the future is low
.
For patients receiving the intensive regimen of CHOEP and hematopoietic stem cell transplantation, although the 5-year OS rate has improved, it still does not exceed 50%, and it is accompanied by early treatment failure, treatment-related side effects, and death
.
Treatment plan optimization 1.
New recommendations in the 2021 guidelines: CHOP or CHOP-like combined with new drugs 2021 NCCN guidelines and 2021 CSCO guidelines proposed in the optimization of first-line treatment.
The treatment of PTCL patients is still on the basis of CHOP and CHOP-like plans, combined with new drugs.
, Such as CD30 monoclonal antibody vebutuximab (BV), HDACi inhibitor romidepsin, antimetabolites pratroxa, immunomodulator lenalidomide and so on
.
In the 2021 NCCN guidelines and 2021 CSCO guidelines released this year, it is pointed out that for ALK+ or ALK- anaplastic large cell lymphoma (ALCL), or other types of CD30+ patients, BV+CHP is recommended, and the remaining patients still prefer CHOEP Or CHOP-like program
.
In the 2021 EHA meeting, the 5-year follow-up results of the ECHELON-2 study provide data support for this guideline update
.
In the study, the median PFS of patients in the BV+CHP treatment group was 62.
26 months, much higher than the 23.
4 months in the CHOP treatment group
.
Some patients receive BV treatment again after the treatment progresses.
Regardless of whether they have received BV treatment in the early stage, they can get a good effect if they receive BV treatment again after the progress
.
Especially for patients who have received BV treatment in the past, 59% of patients still respond to BV treatment again
.
Although more than half of the patients have side effects of peripheral neuropathy, more than 70% of patients will eventually be relieved or improved, and its safety is controllable
.
The conclusion of another large sample study from LYSE pointed out that compared with CHOP, romidepsin combined with CHOP (Ro-CHOP) did not improve patients' PFS and OS, but increased the incidence of hematological toxicity above grade 3 , Leading to a decrease in the completion rate of patients receiving CHOP regimen treatment
.
A domestic small-sample single-center study concluded that Chidamide combined with CHOP (C-CHOP) can effectively prolong PFS, but there is no significant difference in OS and overall response rate (ORR), and the addition of Chidamide Increased hematological toxicity, requiring larger samples and longer follow-up
.
2.
For patients with PTCL other than ALCL, autologous hematopoietic stem cell transplantation is recommended.
In the updated guidelines in 2021, autologous hematopoietic stem cell transplantation is recommended for subtypes other than ALCL
.
A retrospective study in the Netherlands showed that the 5-year OS of patients receiving autologous stem cell transplantation was significantly better than that of patients receiving allogeneic hematopoietic stem cell transplantation
.
After first-line induction, regardless of autologous or allogeneic transplantation, the CR rate increased significantly, but there was no significant difference in disease-free survival (EFS), PFS, and OS
.
Therefore, for young patients in need of transplantation, autologous hematopoietic stem cell transplantation is still the preferred option, and allogeneic transplantation can be used as an optional treatment option after recurrence of autologous transplantation
.
Exploration of relapse and refractory programs 1.
New targeted drugs have achieved good results and provide more treatment options for R/R PTCL patients.
Once PTCL patients have relapse and refractory, their OS is poor, and the median OS after relapse is only 5.
8 months, 3 years OS rate ≤30%
.
For patients entering the back-line treatment, the 2021 NCCN guidelines mentioned that in addition to chemotherapy, some new targeted therapies are recommended, such as the HDACi inhibitor romidepsin, etc.
This year, a new gram for ALK+ ALCL has been added.
Zoltinib, new target drugs such as alemtuzumab
.
At present, a large number of new targeted drugs have been used in the research of PTCL treatment
.
The single-drug treatment of PTCL with new targeted drugs has better curative effect, and the side effects are safe and controllable
.
A retrospective study in the United Kingdom proved that BV treatment has significant survival benefits for patients with relapsed/refractory ALCL.
The earlier the use, the greater the benefit, and it has no obvious relationship with ALK status and age
.
The multi-center, single-arm phase II study of the dual SYK/JAK inhibitor Cerdulatinib monotherapy for relapsed and refractory PTCL showed that the overall response rate of ALCL and PTCL patients with the follicular helper T-cell lymphoma phenotype was higher than that of other subtypes.
Reached 51.
9%
.
The results of a multi-center, single-arm phase II study of farnesyl transferase inhibitor Tipifarnib monotherapy for relapsed and refractory PTCL showed that the ORR of patients was 39.
7%, and the ORRs of ALCL and PTCL-cxcl12+ patients were 56.
3% and 40%, respectively.
A better effect
.
The first human trial of the EZH1/EZH2 dual-target inhibitor Valemetostat in the treatment of R/R PTCL showed an ORR of 54.
5% at a dose of 200 mg.
The ORR of ALCL seems to be slightly better than other subtypes
.
Lacutamab, as the first drug to reduce the expression of KIR3DL2 through antibody-dependent cell-mediated cytotoxicity (ADCC), can be used to treat skin lymphoma
.
A phase II study of Lacutamab in the treatment of advanced mycosis fungoides (MF) at the ICML conference this year showed that Lacutamab only has 45% skin response to KIR3DL2+ MF, and no response to KIR3DL2- at all, and the sample size needs to be expanded
.
In a domestic study of 7 patients with PTCL who were not suitable for autologous hematopoietic stem cell transplantation as maintenance therapy after induction or salvage treatment, 4 patients achieved PR or better curative effect
.
2.
Combination medication is the main trend of future research.
Professor Zhang mentioned that the combination of demethylation drugs and HDACi inhibitors will have a synergistic anti-T cell lymphoma effect
.
In a multi-center phase II clinical study, the combination of azacitidine and romidepsin effectively improved the efficacy of R/R PTCL patients, especially those with follicular helper T cell phenotype.
.
Therefore, for R/R PTCL, the combination of different new drugs is the main trend of future research
.
Summary Professor Zhang concluded at the end that PTCL has a poor prognosis, and due to its low incidence and high heterogeneity, related treatment research is progressing slowly, and new treatment options need to be continuously explored
.
BV combined with chemotherapy significantly prolonged the PFS and OS of patients with CD30+ PTCL, and changed the pattern of first-line treatment for PTCL
.
R/R PTCL clinical treatment options are still being explored, and new targeted drugs will provide more treatment options for R/R PTCL patients
.
The prognosis of different subtypes of PTCL is quite different.
Whether new drugs are used alone or in combination, it is necessary to consider the balance of efficacy and safety.
In the era of precision medicine, comprehensive planning with the help of Biomarker or gene phenotype may bring more benefits to PTCL patients.
Benefit more
.
Professor Zhang Liling, Chief Physician, Doctoral Supervisor, Director of Lymphoma Ward, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Chairman of the Lymphoma Professional Committee of Hubei Anti-Cancer Association, Member of CSCO Anti-Lymphoma Alliance, Member of China Anti-Cancer Association Lymphoma Professional Committee, Zhong Zhong Member of the Cancer Translational Medicine Group of the Oncology Branch of the Medical Association Member of the Standing Committee of the Lymphoma Professional Committee of the Chinese Association of Geriatric Oncology Vice Chairman of the Hubei Provincial Society of Clinical Oncology Lymphoma Professional Committee Designated Chairman Stamp "Read the original text", we make progress together
This conference focuses on research in the field of hematology.
"New progress, new theory, new technology", the latest achievements and experience from basic to clinical, from frontier to practice, strive to comprehensively improve the understanding, screening, diagnosis and treatment of hematology and related diseases of grassroots medical workers
.
At the meeting, Professor Zhang Liling from the Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology gave a report on the topic of "New Progress in Peripheral T-Cell Lymphoma Targeted Therapy and Practice Sharing", respectively, in "Peripheral T-Cell Lymphoma (PTCL) Treatment" In-depth discussion will be carried out in three aspects, “Current situation”, “Optimization of initial treatment plan”, and “Exploration of relapse and refractory treatment plan”
.
This article organizes its main content as follows for the reference of readers
.
Current status of PTCL treatment 1.
The CHOP regimen is still the most common treatment regimen for PTCL.
Currently, the most common clinical treatment regimen for PTCL is still based on CHOP and CHOP-like chemotherapy
.
In Asian countries, CHOP and CHOEP are still the more commonly used regimens for the treatment of PTCL patients, and asparaginase-containing chemotherapy regimens are the mainstay for NK/T-cell lymphoma patients
.
2.
The prognosis of the previous CHOP regimen in first-line treatment is poor, and new treatment options need to be explored.
Professor Zhang said that the prognosis of PTCL patients is poor.
The low incidence and high heterogeneity make treatment progress relatively slow.
At present, most PTCL patients still accept The CHOP or CHOP-like treatment program has a lower complete remission (CR) rate, and poor progression-free survival (PFS) and overall survival (OS)
.
Except for ALK+ALCL, which has a lower IPI score, the 5-year OS rate of other patients is less than 50%, and patients with an IPI score> 2 have a worse prognosis
.
The proportion of relapsed and refractory patients is relatively high, and the long-term survival rate in the future is low
.
For patients receiving the intensive regimen of CHOEP and hematopoietic stem cell transplantation, although the 5-year OS rate has improved, it still does not exceed 50%, and it is accompanied by early treatment failure, treatment-related side effects, and death
.
Treatment plan optimization 1.
New recommendations in the 2021 guidelines: CHOP or CHOP-like combined with new drugs 2021 NCCN guidelines and 2021 CSCO guidelines proposed in the optimization of first-line treatment.
The treatment of PTCL patients is still on the basis of CHOP and CHOP-like plans, combined with new drugs.
, Such as CD30 monoclonal antibody vebutuximab (BV), HDACi inhibitor romidepsin, antimetabolites pratroxa, immunomodulator lenalidomide and so on
.
In the 2021 NCCN guidelines and 2021 CSCO guidelines released this year, it is pointed out that for ALK+ or ALK- anaplastic large cell lymphoma (ALCL), or other types of CD30+ patients, BV+CHP is recommended, and the remaining patients still prefer CHOEP Or CHOP-like program
.
In the 2021 EHA meeting, the 5-year follow-up results of the ECHELON-2 study provide data support for this guideline update
.
In the study, the median PFS of patients in the BV+CHP treatment group was 62.
26 months, much higher than the 23.
4 months in the CHOP treatment group
.
Some patients receive BV treatment again after the treatment progresses.
Regardless of whether they have received BV treatment in the early stage, they can get a good effect if they receive BV treatment again after the progress
.
Especially for patients who have received BV treatment in the past, 59% of patients still respond to BV treatment again
.
Although more than half of the patients have side effects of peripheral neuropathy, more than 70% of patients will eventually be relieved or improved, and its safety is controllable
.
The conclusion of another large sample study from LYSE pointed out that compared with CHOP, romidepsin combined with CHOP (Ro-CHOP) did not improve patients' PFS and OS, but increased the incidence of hematological toxicity above grade 3 , Leading to a decrease in the completion rate of patients receiving CHOP regimen treatment
.
A domestic small-sample single-center study concluded that Chidamide combined with CHOP (C-CHOP) can effectively prolong PFS, but there is no significant difference in OS and overall response rate (ORR), and the addition of Chidamide Increased hematological toxicity, requiring larger samples and longer follow-up
.
2.
For patients with PTCL other than ALCL, autologous hematopoietic stem cell transplantation is recommended.
In the updated guidelines in 2021, autologous hematopoietic stem cell transplantation is recommended for subtypes other than ALCL
.
A retrospective study in the Netherlands showed that the 5-year OS of patients receiving autologous stem cell transplantation was significantly better than that of patients receiving allogeneic hematopoietic stem cell transplantation
.
After first-line induction, regardless of autologous or allogeneic transplantation, the CR rate increased significantly, but there was no significant difference in disease-free survival (EFS), PFS, and OS
.
Therefore, for young patients in need of transplantation, autologous hematopoietic stem cell transplantation is still the preferred option, and allogeneic transplantation can be used as an optional treatment option after recurrence of autologous transplantation
.
Exploration of relapse and refractory programs 1.
New targeted drugs have achieved good results and provide more treatment options for R/R PTCL patients.
Once PTCL patients have relapse and refractory, their OS is poor, and the median OS after relapse is only 5.
8 months, 3 years OS rate ≤30%
.
For patients entering the back-line treatment, the 2021 NCCN guidelines mentioned that in addition to chemotherapy, some new targeted therapies are recommended, such as the HDACi inhibitor romidepsin, etc.
This year, a new gram for ALK+ ALCL has been added.
Zoltinib, new target drugs such as alemtuzumab
.
At present, a large number of new targeted drugs have been used in the research of PTCL treatment
.
The single-drug treatment of PTCL with new targeted drugs has better curative effect, and the side effects are safe and controllable
.
A retrospective study in the United Kingdom proved that BV treatment has significant survival benefits for patients with relapsed/refractory ALCL.
The earlier the use, the greater the benefit, and it has no obvious relationship with ALK status and age
.
The multi-center, single-arm phase II study of the dual SYK/JAK inhibitor Cerdulatinib monotherapy for relapsed and refractory PTCL showed that the overall response rate of ALCL and PTCL patients with the follicular helper T-cell lymphoma phenotype was higher than that of other subtypes.
Reached 51.
9%
.
The results of a multi-center, single-arm phase II study of farnesyl transferase inhibitor Tipifarnib monotherapy for relapsed and refractory PTCL showed that the ORR of patients was 39.
7%, and the ORRs of ALCL and PTCL-cxcl12+ patients were 56.
3% and 40%, respectively.
A better effect
.
The first human trial of the EZH1/EZH2 dual-target inhibitor Valemetostat in the treatment of R/R PTCL showed an ORR of 54.
5% at a dose of 200 mg.
The ORR of ALCL seems to be slightly better than other subtypes
.
Lacutamab, as the first drug to reduce the expression of KIR3DL2 through antibody-dependent cell-mediated cytotoxicity (ADCC), can be used to treat skin lymphoma
.
A phase II study of Lacutamab in the treatment of advanced mycosis fungoides (MF) at the ICML conference this year showed that Lacutamab only has 45% skin response to KIR3DL2+ MF, and no response to KIR3DL2- at all, and the sample size needs to be expanded
.
In a domestic study of 7 patients with PTCL who were not suitable for autologous hematopoietic stem cell transplantation as maintenance therapy after induction or salvage treatment, 4 patients achieved PR or better curative effect
.
2.
Combination medication is the main trend of future research.
Professor Zhang mentioned that the combination of demethylation drugs and HDACi inhibitors will have a synergistic anti-T cell lymphoma effect
.
In a multi-center phase II clinical study, the combination of azacitidine and romidepsin effectively improved the efficacy of R/R PTCL patients, especially those with follicular helper T cell phenotype.
.
Therefore, for R/R PTCL, the combination of different new drugs is the main trend of future research
.
Summary Professor Zhang concluded at the end that PTCL has a poor prognosis, and due to its low incidence and high heterogeneity, related treatment research is progressing slowly, and new treatment options need to be continuously explored
.
BV combined with chemotherapy significantly prolonged the PFS and OS of patients with CD30+ PTCL, and changed the pattern of first-line treatment for PTCL
.
R/R PTCL clinical treatment options are still being explored, and new targeted drugs will provide more treatment options for R/R PTCL patients
.
The prognosis of different subtypes of PTCL is quite different.
Whether new drugs are used alone or in combination, it is necessary to consider the balance of efficacy and safety.
In the era of precision medicine, comprehensive planning with the help of Biomarker or gene phenotype may bring more benefits to PTCL patients.
Benefit more
.
Professor Zhang Liling, Chief Physician, Doctoral Supervisor, Director of Lymphoma Ward, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Chairman of the Lymphoma Professional Committee of Hubei Anti-Cancer Association, Member of CSCO Anti-Lymphoma Alliance, Member of China Anti-Cancer Association Lymphoma Professional Committee, Zhong Zhong Member of the Cancer Translational Medicine Group of the Oncology Branch of the Medical Association Member of the Standing Committee of the Lymphoma Professional Committee of the Chinese Association of Geriatric Oncology Vice Chairman of the Hubei Provincial Society of Clinical Oncology Lymphoma Professional Committee Designated Chairman Stamp "Read the original text", we make progress together
