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Lymphoma is a common malignant tumor originating from the lymphoid hematopoietic system, and it is also one of the tumors with a high incidence in recent years.
The disease control rate and cure rate of lymphoma are relatively high, and the survival period of patients can be greatly prolonged after standardized treatment and management.
In order to further discuss the diagnosis, treatment and development of lymphoma in my country, a series of activities of the Lymphocytic Disease Group of the Hematology Branch of the Chinese Medical Association-the 2nd Bethune Lymphoma Youth Forum in 2021 will be held online on May 29, 2021.
At this meeting, Professor Niu Ting from West China Hospital of Sichuan University gave a theme report on "Diffuse Large B-Cell Lymphoma (DLBCL) Diagnosis and Treatment Progress".
Yimaitong organized the main contents as follows.
The epidemiology and prognostic factors of DLBCL Professor Niu Ting first introduced the epidemiology of DLBCL.
There are approximately 150,000 new cases of DLBCL each year worldwide, accounting for approximately 30% of all non-Hodgkin’s lymphoma (NHL) cases.
The median age of patients with DLBCL at diagnosis is approximately 65 years, and 30% of patients are older than 75 years.
They usually present with progressive lymphadenopathy, extra-lymphatic lesions, or both, and require treatment.
The epidemiological statistics of West China Hospital of Sichuan University show that DLBCL was the NHL with the highest incidence in 2013-2018, with 727 new cases of DLBCL diagnosed each year.
Professor Niu Ting then introduced the prognostic factors of DLBCL.
5%-15% of DLBCL has MYC rearrangement, which can occur simultaneously with BCL2 rearrangement or BCL6 rearrangement, which is called "double-hit (DHL)" or "triple-hit (THL)" lymphoma.
The prognosis of some patients is relatively poor.
The adverse outcome of DHL and THL patients is more obvious when the MYC and IG gene partners have translocations.
The tumor microenvironment also has a significant impact on the prognosis of DLBCL.
A study conducted a transcriptomic analysis of the microenvironment of 4655 DLBCL patients from multiple independent cohorts, describing 4 different lymphoma microenvironments (LME), namely "germinal center type (GC)", " Mesenchymal (MS)", "Inflammatory (IN)", and "Depleted (DP)".
They are closely related to different biological aberrations and clinical behaviors.
There are more GCB subtypes in LME-MS DLBCL patients, and more ABC subtypes in LME-IN DLBCL patients.
The proportion of high-risk DLBCL patients with the four LME subtypes of GC, MS, IN, and DP increased successively, and the proportion of relapse and refractory patients after R-CHOP treatment also increased successively.
Among them, the OS and progression-free survival (PFS) of patients with LME-DP DLBCL ) Is poor.
In addition, the total tumor metabolic volume (TMTV), bone marrow involvement, circulating tumor DNA (ctDNA) level and molecular response in PET/CT imaging also have prognostic significance for DLBCL.
Professor Niu Ting said that the development of related tests has a certain significance for the prognosis of DLBCL patients.
Treatment of DLBCL is limited.
About 30% of DLBCL patients are limited in their treatment.
These patients usually have low-risk clinical features and good outcomes.
The 5-year OS rate is 85%-95%.
The current focus of limited-stage DLBCL research is to limit the number of chemotherapy cycles or omit radiotherapy.
The Phase III FLYER study confirmed that the 6R-4CHOP regimen in young patients with limited-stage DLBCL is not inferior to the standard treatment regimen, and the toxicity is reduced.
At present, the treatment plan has been included in relevant clinical guidelines.
In addition, for the limited-term DLBCL, Professor Niu Ting also emphasized the importance of PET-CT assessment.
A phase II study showed that for patients with complete remission (CR) assessed by PET-CT after 3R-CHOP treatment, a 4-cycle R-CHOP regimen is sufficient.
However, for patients with positive mid-term PET-CT assessment, or patients with high IPI scores and high-risk biological characteristics, the best treatment plan is still inconclusive.
Approximately 70% of DLBCL patients with advanced DLBCL are in the advanced stage at the time of treatment and require systemic treatment.
For these patients, the current standard chemotherapy regimen is the 8R-6CHOP regimen.
As early as 2014, related studies proposed to combine other drugs on the basis of the R-CHOP regimen to further improve the efficacy, but the results of the related studies were all negative, and the R-CHOP+X regimen has no significant breakthrough in DLBCL so far.
In addition, the application of consolidation radiotherapy (RT) in advanced DLBCL is still controversial.
The results of a recently announced study of 723 patients with advanced DLBCL showed that the treatment outcome of PET-CT-positive patients after receiving consolidation RT treatment was close to those of PET-CT-negative patients; PET-CT with a large mass (≥10cm) was present at the time of diagnosis -The prognosis of patients with negative CT is the same as that of patients without huge masses.
PET-CT can reliably guide the selective administration of consolidation RT.
Patients with advanced DLBCL who are negative for PET-CT and have not received RT have a better prognosis.
About 20%-25% of DLBCL patients are not suitable for standard first-line treatment (such as R-CHOP regimen) due to age-related poor health, comorbidities, or cardiac insufficiency.
For this part of unfit DLBCL patients, the results of the GELALNH03-7B study show that R-miniCHOP21 is an effective and safe treatment plan for elderly (>80 years) DLBCL patients with good physical conditions.
A retrospective study in Canada showed that the 10-year PFS rate of the R-CEOP regimen in the treatment of unfit DLBCL patients was not significantly different from the R-CHOP regimen.
The R-CEOP regimen is also an option for these patients.
The central nervous system (CNS) prevents 3%-5% of DLBCL patients from recurring CNS, and the median OS of these patients is less than 6 months.
CNS recurrence often occurs early after treatment, indicating that there are occult central nervous system diseases at the time of diagnosis.
However, the prevention of CNS in the treatment of DLBCL is still controversial, and the effect of CNS prevention with systemic drugs that can enter the CNS has not yet been confirmed.
A retrospective study announced at the 2020 ASH Conference showed that high-dose methotrexate (HD-MTX) and high-intensity immunochemotherapy are not significantly related to the risk of CNS recurrence, PFS and OS, and autologous hematopoietic stem cell transplantation is accepted.
(ASCT) Consolidation therapy can reduce the risk of CNS recurrence.
Among patients with relapsed and refractory DLBCL treated with the R-CHOP regimen, 10%-15% of patients have primary refractory disease (that is, incomplete remission or relapse within 6 months of treatment), and another 20%-25 % Of patients progressed within 2 years after the initial remission (POD24), and this part of the patients had poor treatment outcomes.
Patients with long-term recurrence (>2 years after treatment) have better outcomes, but indolent lymphoma may recur.
For these patients, repeated biopsy is necessary.
For patients with chemotherapy-sensitive relapses or refractory diseases, high-dose chemotherapy and ASCT may bring the disease to cure.
However, due to advanced age and comorbidities, only half of the relapsed and refractory patients are suitable for ASCT.
The advent of chimeric antigen receptor T cell (CAR-T) immunotherapy has brought a major change in the treatment of relapsed and refractory DLBCL.
At present, the FDA has approved a variety of CAR-T products for the treatment of relapsed and refractory DLBCL.
In addition, new types of CAR-Ts such as bispecific CAR-T, tandem CAR-T, and allogeneic CAR-T also have a certain scope for exploration, which is expected to bring more treatment options for relapsed and refractory DLBCL in the future.
In addition to CAR-T therapy, antibody-drug conjugates (ADC), nuclear export protein inhibitors, and CD19 monoclonal antibody are all new drugs worthy of attention in relapsed and refractory DLBCL.
Polatuzumab Vedotin, Selinexor, and Tafasitamab have been approved by the FDA for the treatment of relapsed and refractory DLBCL.
In addition, CD47 blockers and CD20xCD3 bispecific antibodies have also shown initial efficacy in relapsed and refractory DLBCL, and further exploration is needed in the future.
Summary Professor Niu Ting finally concluded: Although there are still unresolved clinical needs for DLBCL, with the continuous improvement of DLBCL molecular typing and the advent of some new drugs, DLBCL patients are expected to have a higher cure rate and better in the future.
The clinical outcome.
Professor Niu Ting, Doctor of Medicine, Chief Physician, Professor, and Doctoral Supervisor, Director of the Department of Hematology, West China Hospital, Sichuan University, Member of the Standing Committee of the Chinese Medical Association Hematology Branch, Deputy Leader of the Lymphocytic Disease Group, Member of the Standing Committee of the Hematological Oncology Committee of the Chinese Anti-Cancer Association Deputy Chairman of the Expert Committee of Hematology Public Welfare Projects of the Health Foundation Deputy Chairman of the Blood Committee of China Medical Education Association, Deputy Chairman of the Hemostasis and Thrombosis Branch, Deputy Chief Editor of the International Journal of Blood Transfusion and Hematology, China Medical Association, National Medical Products Administration External expert of the Drug Evaluation Center, Chairman of the Hematology and Tumor Professional Committee of Sichuan Cancer Society, Chairman of the Hematology Branch of Sichuan Medical Association, and Designate Director of the Sichuan Hematology Medical Quality Control Center, stamped "Read the original text", and we will make progress together
The disease control rate and cure rate of lymphoma are relatively high, and the survival period of patients can be greatly prolonged after standardized treatment and management.
In order to further discuss the diagnosis, treatment and development of lymphoma in my country, a series of activities of the Lymphocytic Disease Group of the Hematology Branch of the Chinese Medical Association-the 2nd Bethune Lymphoma Youth Forum in 2021 will be held online on May 29, 2021.
At this meeting, Professor Niu Ting from West China Hospital of Sichuan University gave a theme report on "Diffuse Large B-Cell Lymphoma (DLBCL) Diagnosis and Treatment Progress".
Yimaitong organized the main contents as follows.
The epidemiology and prognostic factors of DLBCL Professor Niu Ting first introduced the epidemiology of DLBCL.
There are approximately 150,000 new cases of DLBCL each year worldwide, accounting for approximately 30% of all non-Hodgkin’s lymphoma (NHL) cases.
The median age of patients with DLBCL at diagnosis is approximately 65 years, and 30% of patients are older than 75 years.
They usually present with progressive lymphadenopathy, extra-lymphatic lesions, or both, and require treatment.
The epidemiological statistics of West China Hospital of Sichuan University show that DLBCL was the NHL with the highest incidence in 2013-2018, with 727 new cases of DLBCL diagnosed each year.
Professor Niu Ting then introduced the prognostic factors of DLBCL.
5%-15% of DLBCL has MYC rearrangement, which can occur simultaneously with BCL2 rearrangement or BCL6 rearrangement, which is called "double-hit (DHL)" or "triple-hit (THL)" lymphoma.
The prognosis of some patients is relatively poor.
The adverse outcome of DHL and THL patients is more obvious when the MYC and IG gene partners have translocations.
The tumor microenvironment also has a significant impact on the prognosis of DLBCL.
A study conducted a transcriptomic analysis of the microenvironment of 4655 DLBCL patients from multiple independent cohorts, describing 4 different lymphoma microenvironments (LME), namely "germinal center type (GC)", " Mesenchymal (MS)", "Inflammatory (IN)", and "Depleted (DP)".
They are closely related to different biological aberrations and clinical behaviors.
There are more GCB subtypes in LME-MS DLBCL patients, and more ABC subtypes in LME-IN DLBCL patients.
The proportion of high-risk DLBCL patients with the four LME subtypes of GC, MS, IN, and DP increased successively, and the proportion of relapse and refractory patients after R-CHOP treatment also increased successively.
Among them, the OS and progression-free survival (PFS) of patients with LME-DP DLBCL ) Is poor.
In addition, the total tumor metabolic volume (TMTV), bone marrow involvement, circulating tumor DNA (ctDNA) level and molecular response in PET/CT imaging also have prognostic significance for DLBCL.
Professor Niu Ting said that the development of related tests has a certain significance for the prognosis of DLBCL patients.
Treatment of DLBCL is limited.
About 30% of DLBCL patients are limited in their treatment.
These patients usually have low-risk clinical features and good outcomes.
The 5-year OS rate is 85%-95%.
The current focus of limited-stage DLBCL research is to limit the number of chemotherapy cycles or omit radiotherapy.
The Phase III FLYER study confirmed that the 6R-4CHOP regimen in young patients with limited-stage DLBCL is not inferior to the standard treatment regimen, and the toxicity is reduced.
At present, the treatment plan has been included in relevant clinical guidelines.
In addition, for the limited-term DLBCL, Professor Niu Ting also emphasized the importance of PET-CT assessment.
A phase II study showed that for patients with complete remission (CR) assessed by PET-CT after 3R-CHOP treatment, a 4-cycle R-CHOP regimen is sufficient.
However, for patients with positive mid-term PET-CT assessment, or patients with high IPI scores and high-risk biological characteristics, the best treatment plan is still inconclusive.
Approximately 70% of DLBCL patients with advanced DLBCL are in the advanced stage at the time of treatment and require systemic treatment.
For these patients, the current standard chemotherapy regimen is the 8R-6CHOP regimen.
As early as 2014, related studies proposed to combine other drugs on the basis of the R-CHOP regimen to further improve the efficacy, but the results of the related studies were all negative, and the R-CHOP+X regimen has no significant breakthrough in DLBCL so far.
In addition, the application of consolidation radiotherapy (RT) in advanced DLBCL is still controversial.
The results of a recently announced study of 723 patients with advanced DLBCL showed that the treatment outcome of PET-CT-positive patients after receiving consolidation RT treatment was close to those of PET-CT-negative patients; PET-CT with a large mass (≥10cm) was present at the time of diagnosis -The prognosis of patients with negative CT is the same as that of patients without huge masses.
PET-CT can reliably guide the selective administration of consolidation RT.
Patients with advanced DLBCL who are negative for PET-CT and have not received RT have a better prognosis.
About 20%-25% of DLBCL patients are not suitable for standard first-line treatment (such as R-CHOP regimen) due to age-related poor health, comorbidities, or cardiac insufficiency.
For this part of unfit DLBCL patients, the results of the GELALNH03-7B study show that R-miniCHOP21 is an effective and safe treatment plan for elderly (>80 years) DLBCL patients with good physical conditions.
A retrospective study in Canada showed that the 10-year PFS rate of the R-CEOP regimen in the treatment of unfit DLBCL patients was not significantly different from the R-CHOP regimen.
The R-CEOP regimen is also an option for these patients.
The central nervous system (CNS) prevents 3%-5% of DLBCL patients from recurring CNS, and the median OS of these patients is less than 6 months.
CNS recurrence often occurs early after treatment, indicating that there are occult central nervous system diseases at the time of diagnosis.
However, the prevention of CNS in the treatment of DLBCL is still controversial, and the effect of CNS prevention with systemic drugs that can enter the CNS has not yet been confirmed.
A retrospective study announced at the 2020 ASH Conference showed that high-dose methotrexate (HD-MTX) and high-intensity immunochemotherapy are not significantly related to the risk of CNS recurrence, PFS and OS, and autologous hematopoietic stem cell transplantation is accepted.
(ASCT) Consolidation therapy can reduce the risk of CNS recurrence.
Among patients with relapsed and refractory DLBCL treated with the R-CHOP regimen, 10%-15% of patients have primary refractory disease (that is, incomplete remission or relapse within 6 months of treatment), and another 20%-25 % Of patients progressed within 2 years after the initial remission (POD24), and this part of the patients had poor treatment outcomes.
Patients with long-term recurrence (>2 years after treatment) have better outcomes, but indolent lymphoma may recur.
For these patients, repeated biopsy is necessary.
For patients with chemotherapy-sensitive relapses or refractory diseases, high-dose chemotherapy and ASCT may bring the disease to cure.
However, due to advanced age and comorbidities, only half of the relapsed and refractory patients are suitable for ASCT.
The advent of chimeric antigen receptor T cell (CAR-T) immunotherapy has brought a major change in the treatment of relapsed and refractory DLBCL.
At present, the FDA has approved a variety of CAR-T products for the treatment of relapsed and refractory DLBCL.
In addition, new types of CAR-Ts such as bispecific CAR-T, tandem CAR-T, and allogeneic CAR-T also have a certain scope for exploration, which is expected to bring more treatment options for relapsed and refractory DLBCL in the future.
In addition to CAR-T therapy, antibody-drug conjugates (ADC), nuclear export protein inhibitors, and CD19 monoclonal antibody are all new drugs worthy of attention in relapsed and refractory DLBCL.
Polatuzumab Vedotin, Selinexor, and Tafasitamab have been approved by the FDA for the treatment of relapsed and refractory DLBCL.
In addition, CD47 blockers and CD20xCD3 bispecific antibodies have also shown initial efficacy in relapsed and refractory DLBCL, and further exploration is needed in the future.
Summary Professor Niu Ting finally concluded: Although there are still unresolved clinical needs for DLBCL, with the continuous improvement of DLBCL molecular typing and the advent of some new drugs, DLBCL patients are expected to have a higher cure rate and better in the future.
The clinical outcome.
Professor Niu Ting, Doctor of Medicine, Chief Physician, Professor, and Doctoral Supervisor, Director of the Department of Hematology, West China Hospital, Sichuan University, Member of the Standing Committee of the Chinese Medical Association Hematology Branch, Deputy Leader of the Lymphocytic Disease Group, Member of the Standing Committee of the Hematological Oncology Committee of the Chinese Anti-Cancer Association Deputy Chairman of the Expert Committee of Hematology Public Welfare Projects of the Health Foundation Deputy Chairman of the Blood Committee of China Medical Education Association, Deputy Chairman of the Hemostasis and Thrombosis Branch, Deputy Chief Editor of the International Journal of Blood Transfusion and Hematology, China Medical Association, National Medical Products Administration External expert of the Drug Evaluation Center, Chairman of the Hematology and Tumor Professional Committee of Sichuan Cancer Society, Chairman of the Hematology Branch of Sichuan Medical Association, and Designate Director of the Sichuan Hematology Medical Quality Control Center, stamped "Read the original text", and we will make progress together
