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March 19-21, 2021, the 4th China Chronic Lymphocytic Leukemia Conference and the 1st China Chronic Lymphocytic Leukemia Working Group (cwCLL) and International Chronic Lymphocytic Leukemia Working Group ( The iwCLL) joint conference was held online, and a number of hematology experts participated online and offline to share the latest research results of hematology.
At this meeting, Professor Fan Lei from Jiangsu Provincial People's Hospital gave a theme report on "Mantle Cell Lymphoma Diagnosis and Treatment".
Yimaitong organized the main contents as follows.
Overview of mantle cell lymphoma Mantle cell lymphoma (MCL) is a rapidly progressing aggressive lymphoma.
The prognosis of MCL patients is poor, with a median overall survival time of 3-4 years.
Some MCL patients died within 6 months after diagnosis, and only 8% of MCL patients survived for more than 10 years.
More than 90% of MCL patients have extensive lymphadenopathy, splenomegaly, and bone marrow invasion at the time of diagnosis, and the disease has progressed to an advanced stage.
In addition, there is currently no curative treatment plan for MCL, and there is no standard first-line and follow-up treatment plan.
The diagnosis of MCL is currently based on pathological diagnosis as the gold standard.
For MCL similar to leukemia, the MICM classification of leukemia is clinically used for diagnosis.
The flow cytometry immunophenotype of MCL diagnosed is close to that of chronic lymphocytic leukemia, which is prone to misdiagnosis.
MCL has a large heterogeneity.
At present, MCL is divided into three categories: classic MCL, indolent MCL, and in situ mantle cell tumor (ISMCN), of which classic MCL accounts for about 90%.
At present, the MIPI-c score combined with the MIPI score and Ki-67 positive rate is used clinically to judge the prognosis of MCL patients.
Related studies at the 2020 ASH Conference summarized the prognostic factors of MCL.
At present, the prognostic factors of MCL are gradually shifting from clinical prognostic factors to biological prognostic factors and efficacy-related parameters.
First-line treatment of mantle cell lymphoma 01 Indolent MCL related guidelines point out that indolent MCL does not require treatment if there is no indication for treatment, and the patient will be treated after the indication for treatment.
A study published at the 2019 ASH Conference explored early, indolent MCL with no indication for treatment.
The study used dual-targeted first-line therapy of ibrutinib combined with rituximab for these indolent MCL patients.
At a median follow-up of 23 months, the complete response (CR) rate reached 77%, and objective remission was 12 months.
The ORR reached 83%.
However, with the extension of follow-up time, some patients with MCL have turned positive from minimal residual disease (MRD) status.
Therefore, for patients with indolent MCL who have no indications for treatment, a conservative watch-and-wait strategy should still be adopted in treatment.
02 Classic MCL (young patients) Clinically, most MCL patients are young classic MCL patients.
For these patients, high-dose cytarabine chemotherapy combined with rituximab induction therapy, sequential autologous hematopoietic stem cell transplantation ( ASCT).
High-intensity chemotherapy regimens such as R-DHAP regimen or R-HyperCVAD regimen can usually achieve better curative effects and prolong the overall survival (OS) of MCL patients to more than 10 years.
However, the toxic and side effects of high-intensity chemotherapy regimens are also strong, and the bone marrow suppression effect of patients is relatively obvious, and related programs can only be carried out in large hospitals.
Some studies have further explored the treatment options for young classic MCL patients.
The Window study tried to reduce the intensity of chemotherapy in MCL patients during the treatment process, and at the same time added BTK inhibitors to explore the efficacy and safety of this treatment plan in MCL patients.
The results of the study showed that the short-term efficacy of the treatment program was excellent, with an ORR of 100%.
At a median follow-up of 30 months, the PFS rate of MCL patients exceeded 80%, and the OS rate exceeded 95%.
However, the MIPI-c scores of most patients in this study are low-risk, and the efficacy of this treatment plan for patients with high-risk MCL remains to be explored.
Based on the results of a study published in 2005, the main method of consolidation therapy for young classic MCL patients is ASCT.
However, considering that the induction program for MCL patients has been improved from CHOP to rituximab-based chemotherapy in recent years, the necessity of ASCT as a consolidation therapy for MCL patients needs to be further explored.
At the ICML conference in 2019, the results of more than 10 years of follow-up of the above studies were announced.
The results showed that: for MCL patients receiving CHOP induction therapy, ASCT consolidation therapy can still bring benefits in PFS and OS; but for induction therapy.
In patients with MCL undergoing rituximab-based chemotherapy, ASCT consolidation therapy does not improve PFS and OS.
The inclusion of rituximab in the first-line treatment of MCL weakened the position of ASCT in the treatment of MCL.
A single-center, retrospective study published by MD Anderson Cancer Research Center in 2012 showed that: In addition to the poor efficacy of R-CHOP alone, the R-CHOP program is sequential transplantation, R-HyperCVAD program, and R-HyperCVAD program are sequential All transplants have achieved good results.
The results of the study showed that the high-dose cytarabine added in the induction treatment phase would also weaken the status of subsequent ASCT, but for weaker induction treatment programs such as R-CHOP, the subsequent ASCT can make up for the lack of efficacy.
The results of the study announced at the 2020 EHA conference also showed that MCL patients who obtained CR and MRD-negative after first-line treatment had limited benefits for follow-up ASCT.
Professor Fan Lei summarized the results of the above-mentioned multiple studies: Under the background of the current high-dose cytarabine combined with rituximab in the first-line treatment of MCL, the status of ASCT in the first-line treatment of MCL has been weakened.
At present, most guidelines recommend that the maintenance treatment of MCL patients choose rituximab single-agent regimen, but considering the economic situation of domestic MCL patients, other alternative maintenance treatment options are also worth exploring.
The results of the Phase III MCL0208 study announced at the 2018 ASH Conference showed that MCL patients who achieved CR/partial remission (PR) after receiving ASCT, subsequent lenalidomide consolidation therapy can improve PFS (3-year PFS rate: 80% vs 64 %; P=0.
013), but OS did not benefit (93% vs 86%; P=0.
91).
For MCL patients with limited economic conditions, lenalidomide can be used as a consolidation treatment option.
The Triangle study explored the use of BTK inhibitor ibrutinib in the treatment of MCL, and evaluated the efficacy of ibrutinib in MCL induction and maintenance treatment, and whether it may replace ASCT.
The research is still in progress and we look forward to the publication of the research results in the future.
A study announced at the EHA conference in 2020 explored the combined use of multiple new drugs in MCL.
The results of the study showed that the combined regimen of ibrutinib, venacral, and otuzumab was used in the initial treatment of MCL.
The short-term and medium-term efficacy of the patients is excellent, and the negative rate of MRD is 80%, but the long-term efficacy of the combined program still needs to be determined by later follow-up.
03 Classic MCL (elderly patients) About 40% of classic MCL patients are elderly patients and are not suitable for receiving high-dose chemotherapy or ASCT.
At present, relevant clinical guidelines recommend that these patients receive low-intensity chemotherapy such as R-CHOP, and sequential maintenance therapy with rituximab.
Professor Fan Lei said that the emergence of bendamustine has brought major changes to the treatment of elderly patients with classic MCL.
The 5-year follow-up results of the BRIGHT study showed that compared with the R-CHOP regimen, the BR regimen (bendamustine, rituximab) significantly prolonged the PFS of elderly MCL patients, but the prolongation of OS was not significant.
For elderly patients with MCL who cannot tolerate chemotherapy, a single-center, phase II study explored the efficacy of dual-targeted therapy of ibrutinib and rituximab.
The results of the study showed that the short-term curative effect of ibrutinib combined with rituximab was excellent, with ORR exceeding 95% and CR rate exceeding 70%.
At a median follow-up of 33 months, the PFS rate of MCL patients was close to 90%, and the OS rate was close to 95%.
However, the study’s inclusion criteria excluded patients with blast/polymorphic type, Ki-67 ≥50%, and largest tumor diameter ≥10cm.
The combination of ibrutinib and rituximab is effective in high-risk elderly MCL patients.
The efficacy remains to be explored.
SHINE (MCL-3002) clinical research is currently exploring whether the combination of ibrutinib can further improve the efficacy in elderly MCL patients on the basis of the BR program.
We look forward to the publication of the results of this study in the future.
04 High-risk MCL A retrospective study conducted in Europe analyzed the high-risk factors of MCL.
The results of the study showed that: mother cell type, Ki-67≥30%, and p53 mutations are high-risk factors for MCL.
In the real world, more than 60% of MCL patients are high-risk patients, and the overall prognosis is poor.
The study also analyzed the treatment options for high-risk MCL patients.
The results of the study showed that the intensive treatment of high-dose cytarabine is more effective in high-risk MCL patients than the lower-intensity R-CHOP and other treatment options.
In the absence of alternative new drugs, intensive treatment can solve part of the treatment needs of patients with high-risk MCL.
A single-center retrospective study conducted in the United States showed that compared with the R-CHOP regimen and high-dose cytarabine intensive treatment, the R2 regimen (rituximab, lenalidomide) is effective in high-risk MCL with TP53 mutations.
Better curative effect was obtained in patients.
Considering the small number of cases included in this retrospective study, the efficacy of the R2 regimen in high-risk MCL patients with TP53 mutations still needs to be further verified by follow-up studies.
For the treatment of relapsed and refractory mantle cell lymphoma, Professor Fan Lei said that MCL is one of the worst prognostic subtypes of all non-Hodgkin's lymphomas (NHL), and there is currently no cure.
Although the first-line treatment of MCL has a high remission rate (60%-97%), most patients will relapse over time.
The treatment of relapsed and refractory MCL is still a clinical problem.
The second-line treatment options for MCL currently include: non-cross-resistance to the previous treatment, new drugs/chemotherapy, and cell therapy.
After remission, young patients can consider low-dose pretreatment regimen of allogeneic hematopoietic stem cell transplantation (RIC-Allo-HSCT).
).
The MAGNIFY study explored the efficacy of the R2 regimen in patients with relapsed and refractory MCL.
The results showed that the R2 regimen had an ORR of 54% in relapsed and refractory MCL, a CR rate of 38%, and a median PFS of 10.
6 months.
For older patients with relapsed and refractory MCL who cannot tolerate high-intensity chemotherapy in second-line therapy, R2 is a better treatment option.
Both the PCYC1104 study and the RAY study showed that Ibrutinib alone has a good effect in relapsed and refractory MCL.
The ORR is about 70%, but the CR rate is relatively low, about 20%, and the median PFS is about 12- 15 months.
Therefore, the single-drug regimen of ibrutinib cannot fully meet all the treatment needs of patients with relapsed and refractory MCL, and is more suitable as a bridging regimen.
The new generation of BTK inhibitor Zebutinib has shown good efficacy in relapsed and refractory MCL.
Relevant studies have shown that the ORR of Zebutinib as a single agent in the treatment of relapsed and refractory MCL reached 84%, and the CR rate reached 78%.
The PFS reached 22.
1 months.
The combination of Bcl-2 inhibitor venecla and ibrutinib has also achieved good efficacy in relapsed and refractory MCL.
Relevant studies have shown that the ORR of the combined regimen is close to 80%, and the CR rate is more than 50%.
At the same time, the combined program significantly prolonged the PFS of patients with relapsed and refractory MCL to 30 months.
The subgroup analysis of the study showed that the combination regimen can also quickly achieve deep remission in patients with TP53 mutations, but for patients with SMARCA4 mutations, the efficacy of this regimen is relatively poor, with a median OS of less than 6 months.
With the advancement of new drugs in the use of MCL, they gradually replace chemotherapy in first-line treatment.
A study conducted in Italy explored the efficacy of traditional chemotherapy in patients with refractory MCL who returned to treatment after first-line treatment with new drugs.
The results of the study showed that the R-BAC chemotherapy regimen (rituximab, bendamustine, cytarabine) achieved 83% ORR, CR rate 60%, and PFS in MCL patients after BTK inhibitor treatment failed.
Up to 10 months.
In the era of new drugs, traditional chemotherapy is also a feasible treatment option for patients with relapsed and refractory MCL.
Chimeric antigen receptor (CAR)-T cell therapy has been the focus of attention for B-cell lymphoma in recent years.
The ZUMA-2 study announced the short-term and long-term follow-up results at the 2020 ASH conference and the 2021 EBMT conference: CAR-T therapy KTE-X19 targeting CD19 has excellent short-term efficacy in relapsed and refractory MCL, with an ORR of 93%.
The CR rate reached 67%.
The long-term efficacy of KTE-X19 in relapsed and refractory MCL is also maintained at a good level.
The expected 15-month PFS rate is 59.
2%, and the OS rate is 76%.
For MCL patients who have failed multi-line therapy, RIC-Allo-HSCT is also an effective treatment option.
A retrospective study published in the United Kingdom in 2018 showed that the 2-year PFS rate of RIC-Allo-HSCT in relapsed and refractory MCL was 61%, and the 2-year OS rate was 78%.
TP53 mutation does not affect the survival of MCL patients receiving RIC-Allo-HSCT.
RIC-Allo-HSCT may be able to overcome the poor prognosis caused by TP53 mutation.
Summary Professor Fan Lei concluded: MIPI and Ki67 are still commonly used clinical prognosis models for MCL, and the clinical value of the new prognostic model is still in the exploratory stage.
MCL requires stratified and individualized treatment.
We recommend high-intensity chemotherapy ± autologous stem cell transplantation ± rituximab maintenance for young patients with MCL as a first-line treatment plan; for elderly patients with MCL, low-intensity therapy and sequential rituximab can be used Anti-maintenance therapy strategy.
New drugs represented by BTK inhibitors, venacola, and lenalidomide have outstanding efficacy in relapsed and refractory MCL, and will gradually be integrated into the first-line treatment.
Professor Fan Lei, Deputy Director of the Department of Hematology, Jiangsu Provincial People's Hospital, Doctor of Medicine, Chief Physician, Associate Professor, The First Youth Standing Council Member of the Chinese Anti-Cancer Association Member of the Hematological Oncology Professional Committee of the Chinese Anti-Cancer Association The 11th Youth Member of the Hematology Branch of the Chinese Medical Association Jiangsu Deputy Chairman of the Youth Committee of the Blood Branch of the Provincial Medical Association, New York, the United States, and the New York Presbyterian Hospital affiliated to Cornell University, the postdoctoral research direction is the precise diagnosis and treatment of lymphatic tumors.
"Read the original text", we make progress together
At this meeting, Professor Fan Lei from Jiangsu Provincial People's Hospital gave a theme report on "Mantle Cell Lymphoma Diagnosis and Treatment".
Yimaitong organized the main contents as follows.
Overview of mantle cell lymphoma Mantle cell lymphoma (MCL) is a rapidly progressing aggressive lymphoma.
The prognosis of MCL patients is poor, with a median overall survival time of 3-4 years.
Some MCL patients died within 6 months after diagnosis, and only 8% of MCL patients survived for more than 10 years.
More than 90% of MCL patients have extensive lymphadenopathy, splenomegaly, and bone marrow invasion at the time of diagnosis, and the disease has progressed to an advanced stage.
In addition, there is currently no curative treatment plan for MCL, and there is no standard first-line and follow-up treatment plan.
The diagnosis of MCL is currently based on pathological diagnosis as the gold standard.
For MCL similar to leukemia, the MICM classification of leukemia is clinically used for diagnosis.
The flow cytometry immunophenotype of MCL diagnosed is close to that of chronic lymphocytic leukemia, which is prone to misdiagnosis.
MCL has a large heterogeneity.
At present, MCL is divided into three categories: classic MCL, indolent MCL, and in situ mantle cell tumor (ISMCN), of which classic MCL accounts for about 90%.
At present, the MIPI-c score combined with the MIPI score and Ki-67 positive rate is used clinically to judge the prognosis of MCL patients.
Related studies at the 2020 ASH Conference summarized the prognostic factors of MCL.
At present, the prognostic factors of MCL are gradually shifting from clinical prognostic factors to biological prognostic factors and efficacy-related parameters.
First-line treatment of mantle cell lymphoma 01 Indolent MCL related guidelines point out that indolent MCL does not require treatment if there is no indication for treatment, and the patient will be treated after the indication for treatment.
A study published at the 2019 ASH Conference explored early, indolent MCL with no indication for treatment.
The study used dual-targeted first-line therapy of ibrutinib combined with rituximab for these indolent MCL patients.
At a median follow-up of 23 months, the complete response (CR) rate reached 77%, and objective remission was 12 months.
The ORR reached 83%.
However, with the extension of follow-up time, some patients with MCL have turned positive from minimal residual disease (MRD) status.
Therefore, for patients with indolent MCL who have no indications for treatment, a conservative watch-and-wait strategy should still be adopted in treatment.
02 Classic MCL (young patients) Clinically, most MCL patients are young classic MCL patients.
For these patients, high-dose cytarabine chemotherapy combined with rituximab induction therapy, sequential autologous hematopoietic stem cell transplantation ( ASCT).
High-intensity chemotherapy regimens such as R-DHAP regimen or R-HyperCVAD regimen can usually achieve better curative effects and prolong the overall survival (OS) of MCL patients to more than 10 years.
However, the toxic and side effects of high-intensity chemotherapy regimens are also strong, and the bone marrow suppression effect of patients is relatively obvious, and related programs can only be carried out in large hospitals.
Some studies have further explored the treatment options for young classic MCL patients.
The Window study tried to reduce the intensity of chemotherapy in MCL patients during the treatment process, and at the same time added BTK inhibitors to explore the efficacy and safety of this treatment plan in MCL patients.
The results of the study showed that the short-term efficacy of the treatment program was excellent, with an ORR of 100%.
At a median follow-up of 30 months, the PFS rate of MCL patients exceeded 80%, and the OS rate exceeded 95%.
However, the MIPI-c scores of most patients in this study are low-risk, and the efficacy of this treatment plan for patients with high-risk MCL remains to be explored.
Based on the results of a study published in 2005, the main method of consolidation therapy for young classic MCL patients is ASCT.
However, considering that the induction program for MCL patients has been improved from CHOP to rituximab-based chemotherapy in recent years, the necessity of ASCT as a consolidation therapy for MCL patients needs to be further explored.
At the ICML conference in 2019, the results of more than 10 years of follow-up of the above studies were announced.
The results showed that: for MCL patients receiving CHOP induction therapy, ASCT consolidation therapy can still bring benefits in PFS and OS; but for induction therapy.
In patients with MCL undergoing rituximab-based chemotherapy, ASCT consolidation therapy does not improve PFS and OS.
The inclusion of rituximab in the first-line treatment of MCL weakened the position of ASCT in the treatment of MCL.
A single-center, retrospective study published by MD Anderson Cancer Research Center in 2012 showed that: In addition to the poor efficacy of R-CHOP alone, the R-CHOP program is sequential transplantation, R-HyperCVAD program, and R-HyperCVAD program are sequential All transplants have achieved good results.
The results of the study showed that the high-dose cytarabine added in the induction treatment phase would also weaken the status of subsequent ASCT, but for weaker induction treatment programs such as R-CHOP, the subsequent ASCT can make up for the lack of efficacy.
The results of the study announced at the 2020 EHA conference also showed that MCL patients who obtained CR and MRD-negative after first-line treatment had limited benefits for follow-up ASCT.
Professor Fan Lei summarized the results of the above-mentioned multiple studies: Under the background of the current high-dose cytarabine combined with rituximab in the first-line treatment of MCL, the status of ASCT in the first-line treatment of MCL has been weakened.
At present, most guidelines recommend that the maintenance treatment of MCL patients choose rituximab single-agent regimen, but considering the economic situation of domestic MCL patients, other alternative maintenance treatment options are also worth exploring.
The results of the Phase III MCL0208 study announced at the 2018 ASH Conference showed that MCL patients who achieved CR/partial remission (PR) after receiving ASCT, subsequent lenalidomide consolidation therapy can improve PFS (3-year PFS rate: 80% vs 64 %; P=0.
013), but OS did not benefit (93% vs 86%; P=0.
91).
For MCL patients with limited economic conditions, lenalidomide can be used as a consolidation treatment option.
The Triangle study explored the use of BTK inhibitor ibrutinib in the treatment of MCL, and evaluated the efficacy of ibrutinib in MCL induction and maintenance treatment, and whether it may replace ASCT.
The research is still in progress and we look forward to the publication of the research results in the future.
A study announced at the EHA conference in 2020 explored the combined use of multiple new drugs in MCL.
The results of the study showed that the combined regimen of ibrutinib, venacral, and otuzumab was used in the initial treatment of MCL.
The short-term and medium-term efficacy of the patients is excellent, and the negative rate of MRD is 80%, but the long-term efficacy of the combined program still needs to be determined by later follow-up.
03 Classic MCL (elderly patients) About 40% of classic MCL patients are elderly patients and are not suitable for receiving high-dose chemotherapy or ASCT.
At present, relevant clinical guidelines recommend that these patients receive low-intensity chemotherapy such as R-CHOP, and sequential maintenance therapy with rituximab.
Professor Fan Lei said that the emergence of bendamustine has brought major changes to the treatment of elderly patients with classic MCL.
The 5-year follow-up results of the BRIGHT study showed that compared with the R-CHOP regimen, the BR regimen (bendamustine, rituximab) significantly prolonged the PFS of elderly MCL patients, but the prolongation of OS was not significant.
For elderly patients with MCL who cannot tolerate chemotherapy, a single-center, phase II study explored the efficacy of dual-targeted therapy of ibrutinib and rituximab.
The results of the study showed that the short-term curative effect of ibrutinib combined with rituximab was excellent, with ORR exceeding 95% and CR rate exceeding 70%.
At a median follow-up of 33 months, the PFS rate of MCL patients was close to 90%, and the OS rate was close to 95%.
However, the study’s inclusion criteria excluded patients with blast/polymorphic type, Ki-67 ≥50%, and largest tumor diameter ≥10cm.
The combination of ibrutinib and rituximab is effective in high-risk elderly MCL patients.
The efficacy remains to be explored.
SHINE (MCL-3002) clinical research is currently exploring whether the combination of ibrutinib can further improve the efficacy in elderly MCL patients on the basis of the BR program.
We look forward to the publication of the results of this study in the future.
04 High-risk MCL A retrospective study conducted in Europe analyzed the high-risk factors of MCL.
The results of the study showed that: mother cell type, Ki-67≥30%, and p53 mutations are high-risk factors for MCL.
In the real world, more than 60% of MCL patients are high-risk patients, and the overall prognosis is poor.
The study also analyzed the treatment options for high-risk MCL patients.
The results of the study showed that the intensive treatment of high-dose cytarabine is more effective in high-risk MCL patients than the lower-intensity R-CHOP and other treatment options.
In the absence of alternative new drugs, intensive treatment can solve part of the treatment needs of patients with high-risk MCL.
A single-center retrospective study conducted in the United States showed that compared with the R-CHOP regimen and high-dose cytarabine intensive treatment, the R2 regimen (rituximab, lenalidomide) is effective in high-risk MCL with TP53 mutations.
Better curative effect was obtained in patients.
Considering the small number of cases included in this retrospective study, the efficacy of the R2 regimen in high-risk MCL patients with TP53 mutations still needs to be further verified by follow-up studies.
For the treatment of relapsed and refractory mantle cell lymphoma, Professor Fan Lei said that MCL is one of the worst prognostic subtypes of all non-Hodgkin's lymphomas (NHL), and there is currently no cure.
Although the first-line treatment of MCL has a high remission rate (60%-97%), most patients will relapse over time.
The treatment of relapsed and refractory MCL is still a clinical problem.
The second-line treatment options for MCL currently include: non-cross-resistance to the previous treatment, new drugs/chemotherapy, and cell therapy.
After remission, young patients can consider low-dose pretreatment regimen of allogeneic hematopoietic stem cell transplantation (RIC-Allo-HSCT).
).
The MAGNIFY study explored the efficacy of the R2 regimen in patients with relapsed and refractory MCL.
The results showed that the R2 regimen had an ORR of 54% in relapsed and refractory MCL, a CR rate of 38%, and a median PFS of 10.
6 months.
For older patients with relapsed and refractory MCL who cannot tolerate high-intensity chemotherapy in second-line therapy, R2 is a better treatment option.
Both the PCYC1104 study and the RAY study showed that Ibrutinib alone has a good effect in relapsed and refractory MCL.
The ORR is about 70%, but the CR rate is relatively low, about 20%, and the median PFS is about 12- 15 months.
Therefore, the single-drug regimen of ibrutinib cannot fully meet all the treatment needs of patients with relapsed and refractory MCL, and is more suitable as a bridging regimen.
The new generation of BTK inhibitor Zebutinib has shown good efficacy in relapsed and refractory MCL.
Relevant studies have shown that the ORR of Zebutinib as a single agent in the treatment of relapsed and refractory MCL reached 84%, and the CR rate reached 78%.
The PFS reached 22.
1 months.
The combination of Bcl-2 inhibitor venecla and ibrutinib has also achieved good efficacy in relapsed and refractory MCL.
Relevant studies have shown that the ORR of the combined regimen is close to 80%, and the CR rate is more than 50%.
At the same time, the combined program significantly prolonged the PFS of patients with relapsed and refractory MCL to 30 months.
The subgroup analysis of the study showed that the combination regimen can also quickly achieve deep remission in patients with TP53 mutations, but for patients with SMARCA4 mutations, the efficacy of this regimen is relatively poor, with a median OS of less than 6 months.
With the advancement of new drugs in the use of MCL, they gradually replace chemotherapy in first-line treatment.
A study conducted in Italy explored the efficacy of traditional chemotherapy in patients with refractory MCL who returned to treatment after first-line treatment with new drugs.
The results of the study showed that the R-BAC chemotherapy regimen (rituximab, bendamustine, cytarabine) achieved 83% ORR, CR rate 60%, and PFS in MCL patients after BTK inhibitor treatment failed.
Up to 10 months.
In the era of new drugs, traditional chemotherapy is also a feasible treatment option for patients with relapsed and refractory MCL.
Chimeric antigen receptor (CAR)-T cell therapy has been the focus of attention for B-cell lymphoma in recent years.
The ZUMA-2 study announced the short-term and long-term follow-up results at the 2020 ASH conference and the 2021 EBMT conference: CAR-T therapy KTE-X19 targeting CD19 has excellent short-term efficacy in relapsed and refractory MCL, with an ORR of 93%.
The CR rate reached 67%.
The long-term efficacy of KTE-X19 in relapsed and refractory MCL is also maintained at a good level.
The expected 15-month PFS rate is 59.
2%, and the OS rate is 76%.
For MCL patients who have failed multi-line therapy, RIC-Allo-HSCT is also an effective treatment option.
A retrospective study published in the United Kingdom in 2018 showed that the 2-year PFS rate of RIC-Allo-HSCT in relapsed and refractory MCL was 61%, and the 2-year OS rate was 78%.
TP53 mutation does not affect the survival of MCL patients receiving RIC-Allo-HSCT.
RIC-Allo-HSCT may be able to overcome the poor prognosis caused by TP53 mutation.
Summary Professor Fan Lei concluded: MIPI and Ki67 are still commonly used clinical prognosis models for MCL, and the clinical value of the new prognostic model is still in the exploratory stage.
MCL requires stratified and individualized treatment.
We recommend high-intensity chemotherapy ± autologous stem cell transplantation ± rituximab maintenance for young patients with MCL as a first-line treatment plan; for elderly patients with MCL, low-intensity therapy and sequential rituximab can be used Anti-maintenance therapy strategy.
New drugs represented by BTK inhibitors, venacola, and lenalidomide have outstanding efficacy in relapsed and refractory MCL, and will gradually be integrated into the first-line treatment.
Professor Fan Lei, Deputy Director of the Department of Hematology, Jiangsu Provincial People's Hospital, Doctor of Medicine, Chief Physician, Associate Professor, The First Youth Standing Council Member of the Chinese Anti-Cancer Association Member of the Hematological Oncology Professional Committee of the Chinese Anti-Cancer Association The 11th Youth Member of the Hematology Branch of the Chinese Medical Association Jiangsu Deputy Chairman of the Youth Committee of the Blood Branch of the Provincial Medical Association, New York, the United States, and the New York Presbyterian Hospital affiliated to Cornell University, the postdoctoral research direction is the precise diagnosis and treatment of lymphatic tumors.
"Read the original text", we make progress together
