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Burkitt’s lymphoma (BL) is a highly aggressive B-cell lymphoma that accounts for approximately 1% of adult lymphomas and 30% of childhood lymphomas
.
Except in the United States, BL usually occurs in local clusters and may be related to immunodeficiency
.
Most BL patients can be cured after receiving short-term, dose-dense immunochemotherapy
.
Although the molecular characteristics of BL have been fully elucidated, there is no feasible targeted therapy option
.
About 90% of patients have MYC rearrangement with immunoglobulin gene mutations (including IGH-MYC t(8;14), IGK, IGL), but the karyotype abnormality of BL is less than that of other high-grade lymphomas
.
Commonly mutated genes include central blast transcription factor TCF3 (25%, activating mutation), its inhibitor ID3 (60%, inactivating mutation), cell cycle regulator CCND3 (30%), CDKN2A/B (10%), TP53(35%)
.
It is worth noting that the PI3K-AKT-mTOR signaling pathway helps BL cells continue to survive
.
The impact of specific molecular characteristics on the prognosis of BL is still unclear
.
Modern prognostic treatment schemes stratify BL according to disease risk, and low-risk BL patients can be treated with simplified schemes
.
Low-risk BL usually presents as a single (sometimes larger) tumor, usually in the cecum
.
Different clinical trials have different specific definitions of low-risk BL, which usually include good physical status, ie ECOG score <2 points, local disease (stage I/II or completely resected abdominal mass), and normal serum lactate dehydrogenase (LDH) levels , Non-giant tumors (<10cm or <7cm)
.
Only about 8%-13% of patients in the clinic meet the low-risk criteria
.
A randomized clinical trial in France (LMBA02) stratifies patients with BL according to age (<40 years, 40-60 years, >60 years), whether there is central nervous system (CNS) or bone marrow involvement, and gives corresponding treatments Scheme
.
The results of the study showed that about 90% of patients achieved complete remission (CR) after stratified treatment, the 3-year progression-free survival (PFS) rate was 64%-95%, and the 3-year overall survival (OS) rate was 71%-100 %
.
A large observational cohort study included 641 BL patients from 30 centers in the United States from 2009 to 2018.
The results showed that the 3-year PFS rate of BL patients was 64%, and the 3-year OS rate was 70%
.
The poor prognostic factors of BL patients include: age ≥ 40 years, poor physical status (ECOG ≥ 2 points), LDH higher than three times the upper limit of normal, and CNS involvement
.
It is worth noting that the use of modern treatment models has not improved the impact of HIV status, disease stage, and MYC rearrangement on the prognosis of BL patients
.
Based on the above observational study data, the researchers designed the BL International Prognostic Index (BL-IPI) and verified it in 457 BL patients in Europe, Canada, and Australia
.
BL-IPI includes 4 independent risk factors, and BL patients are divided into 3 risk groups: the low-risk group (0 risk factors, accounting for 18%), the 3-year PFS rate is 92%-96%; the medium-risk group (1 Three risk factors, accounting for 36%), the 3-year PFS rate was 72%-82%; for the high-risk group (≥2 risk factors, accounting for 46%), the 3-year PFS rate was 53%-63%
.
Since BL-IPI is derived from BL patients receiving standard treatment, it is still not suitable for guiding BL treatment at present
.
However, BL-IPI can be used to stratify patients in related clinical trials in the future to guide management strategies
.
Treatment There are currently several intensive immunochemotherapy regimens combined with CNS prevention that can be used to treat BL (see Table 1 for details), but there are no randomized controlled clinical trials to compare relevant regimens, and the choice of treatment for patients with BL still depends on the preference of the doctor
.
High-intensity treatment regimens are highly toxic to BL patients older than 60 years old.
For these patients, individualized treatment regimens need to be developed
.
The results of the Phase III LMBA02 study showed that combined with rituximab on the basis of immunochemotherapy can significantly improve the event-free survival (EFS; HR: 0.
59; 95% CI: 0.
38-0.
94) and OS of BL patients.
Therefore, it is currently beneficial Tuximab's immunochemotherapy regimen has been included in the standard treatment of BL
.
Table 1: The most commonly used immunochemotherapy regimens for BL
.
Remarks: CR: complete remission; EFS: event-free survival; NR: not reported; PFS: progression-free survival; y: years
.
Regardless of the treatment plan adopted, the following management principles can help improve the cure rate of BL patients: Management of acute complications at the beginning of treatment.
Common acute complications in the initial stage of BL treatment include organ dysfunction, tumor lysis syndrome, and blood cells.
Reduced symptoms, CNS involvement, and/or poor performance status
.
Short-term corticosteroids (such as prednisone 60mg/m2 or dexamethasone 20mg/d) ± cyclophosphamide (200 mg/m2/d) can reduce the incidence of death related to the first cycle of treatment
.
Supportive treatment and timely treatment should be supplemented with growth factors, preventive antibiotics and antiviral drugs, frequent monitoring, and active management of adverse reactions during the process of intensive chemotherapy
.
Part of the treatment is best managed in a large center
.
In the real world, the treatment-related mortality of BL patients is 10%, and the most common cause of death is sepsis or gastrointestinal perforation
.
About 19% of BL patients with CNS-guided treatment have CNS involvement (usually pia mater), which requires lumbar puncture ± CNS imaging for CNS staging
.
Patients with significant CNS involvement require careful management
.
Systemic therapy drugs that can penetrate the blood-brain barrier (high-dose methotrexate, cytarabine, ifosfamide) may reduce the risk of CNS recurrence, and are the first choice for BL patients with brain parenchymal CNS involvement
.
The NCCN guidelines recommend 3 immunochemotherapy regimens for the treatment of BL: R-CODOX-M/IVAC regimen, R-hyperCVAD/MA regimen, DA-EPOCH-R regimen
.
R-hyperCVAD/MA has a higher treatment-related mortality rate (11% vs 5%-8%), which may be due to the longer treatment time
.
The R-CODOX-M±IVAC regimen has a shorter treatment time, and can effectively cover the CNS even when the patient has brain parenchymal CNS disease, and allows outpatient administration with lower toxicity
.
The efficacy of the low-intensity DA-EPOCH-R regimen has been verified in a multi-center, phase II clinical trial
.
The 5-year EFS rate of the low-intensity DA-EPOCH-R regimen in this study was 85%
.
It is worth noting that the low-risk BL patients in the study did not receive preventive treatment for the CNS, and the EFS rate reached 100% after 3 treatment cycles.
There are still many unmet clinical needs in patients with relapsed and refractory BL.
The overall prognosis of this part of patients is poor, and there is a lack of disease-specific data
.
Most patients with BL have a rapid recurrence and usually involve the CNS.
Some patients with relapsed and refractory BL may be sensitive to salvage chemotherapy
.
The efficacy of chimeric antigen receptor T cell (CAR-T) immunotherapy, antibody-drug conjugates, bispecific antibodies, and related targeted drugs in patients with relapse and refractory remains to be verified
.
Summary The current prognostic model of BL relies on clinical indicators related to disease burden, and its accuracy is limited
.
It is necessary to further optimize the BL prognosis model, and to further determine the factors related to disease recurrence through related studies
.
Low-risk BL can be cured by the simplified DA-EPOCH-R regimen
.
The efficacy of DA-EPOCH-R program combined with related targeted drugs in high-risk BL patients needs to be further explored through research
.
Reference source: 1.
Adam J Olszewski, et al.
2021 SOHO.
EXABS-108-NHL.
Stamp "read the original text", we make progress together
.
Except in the United States, BL usually occurs in local clusters and may be related to immunodeficiency
.
Most BL patients can be cured after receiving short-term, dose-dense immunochemotherapy
.
Although the molecular characteristics of BL have been fully elucidated, there is no feasible targeted therapy option
.
About 90% of patients have MYC rearrangement with immunoglobulin gene mutations (including IGH-MYC t(8;14), IGK, IGL), but the karyotype abnormality of BL is less than that of other high-grade lymphomas
.
Commonly mutated genes include central blast transcription factor TCF3 (25%, activating mutation), its inhibitor ID3 (60%, inactivating mutation), cell cycle regulator CCND3 (30%), CDKN2A/B (10%), TP53(35%)
.
It is worth noting that the PI3K-AKT-mTOR signaling pathway helps BL cells continue to survive
.
The impact of specific molecular characteristics on the prognosis of BL is still unclear
.
Modern prognostic treatment schemes stratify BL according to disease risk, and low-risk BL patients can be treated with simplified schemes
.
Low-risk BL usually presents as a single (sometimes larger) tumor, usually in the cecum
.
Different clinical trials have different specific definitions of low-risk BL, which usually include good physical status, ie ECOG score <2 points, local disease (stage I/II or completely resected abdominal mass), and normal serum lactate dehydrogenase (LDH) levels , Non-giant tumors (<10cm or <7cm)
.
Only about 8%-13% of patients in the clinic meet the low-risk criteria
.
A randomized clinical trial in France (LMBA02) stratifies patients with BL according to age (<40 years, 40-60 years, >60 years), whether there is central nervous system (CNS) or bone marrow involvement, and gives corresponding treatments Scheme
.
The results of the study showed that about 90% of patients achieved complete remission (CR) after stratified treatment, the 3-year progression-free survival (PFS) rate was 64%-95%, and the 3-year overall survival (OS) rate was 71%-100 %
.
A large observational cohort study included 641 BL patients from 30 centers in the United States from 2009 to 2018.
The results showed that the 3-year PFS rate of BL patients was 64%, and the 3-year OS rate was 70%
.
The poor prognostic factors of BL patients include: age ≥ 40 years, poor physical status (ECOG ≥ 2 points), LDH higher than three times the upper limit of normal, and CNS involvement
.
It is worth noting that the use of modern treatment models has not improved the impact of HIV status, disease stage, and MYC rearrangement on the prognosis of BL patients
.
Based on the above observational study data, the researchers designed the BL International Prognostic Index (BL-IPI) and verified it in 457 BL patients in Europe, Canada, and Australia
.
BL-IPI includes 4 independent risk factors, and BL patients are divided into 3 risk groups: the low-risk group (0 risk factors, accounting for 18%), the 3-year PFS rate is 92%-96%; the medium-risk group (1 Three risk factors, accounting for 36%), the 3-year PFS rate was 72%-82%; for the high-risk group (≥2 risk factors, accounting for 46%), the 3-year PFS rate was 53%-63%
.
Since BL-IPI is derived from BL patients receiving standard treatment, it is still not suitable for guiding BL treatment at present
.
However, BL-IPI can be used to stratify patients in related clinical trials in the future to guide management strategies
.
Treatment There are currently several intensive immunochemotherapy regimens combined with CNS prevention that can be used to treat BL (see Table 1 for details), but there are no randomized controlled clinical trials to compare relevant regimens, and the choice of treatment for patients with BL still depends on the preference of the doctor
.
High-intensity treatment regimens are highly toxic to BL patients older than 60 years old.
For these patients, individualized treatment regimens need to be developed
.
The results of the Phase III LMBA02 study showed that combined with rituximab on the basis of immunochemotherapy can significantly improve the event-free survival (EFS; HR: 0.
59; 95% CI: 0.
38-0.
94) and OS of BL patients.
Therefore, it is currently beneficial Tuximab's immunochemotherapy regimen has been included in the standard treatment of BL
.
Table 1: The most commonly used immunochemotherapy regimens for BL
.
Remarks: CR: complete remission; EFS: event-free survival; NR: not reported; PFS: progression-free survival; y: years
.
Regardless of the treatment plan adopted, the following management principles can help improve the cure rate of BL patients: Management of acute complications at the beginning of treatment.
Common acute complications in the initial stage of BL treatment include organ dysfunction, tumor lysis syndrome, and blood cells.
Reduced symptoms, CNS involvement, and/or poor performance status
.
Short-term corticosteroids (such as prednisone 60mg/m2 or dexamethasone 20mg/d) ± cyclophosphamide (200 mg/m2/d) can reduce the incidence of death related to the first cycle of treatment
.
Supportive treatment and timely treatment should be supplemented with growth factors, preventive antibiotics and antiviral drugs, frequent monitoring, and active management of adverse reactions during the process of intensive chemotherapy
.
Part of the treatment is best managed in a large center
.
In the real world, the treatment-related mortality of BL patients is 10%, and the most common cause of death is sepsis or gastrointestinal perforation
.
About 19% of BL patients with CNS-guided treatment have CNS involvement (usually pia mater), which requires lumbar puncture ± CNS imaging for CNS staging
.
Patients with significant CNS involvement require careful management
.
Systemic therapy drugs that can penetrate the blood-brain barrier (high-dose methotrexate, cytarabine, ifosfamide) may reduce the risk of CNS recurrence, and are the first choice for BL patients with brain parenchymal CNS involvement
.
The NCCN guidelines recommend 3 immunochemotherapy regimens for the treatment of BL: R-CODOX-M/IVAC regimen, R-hyperCVAD/MA regimen, DA-EPOCH-R regimen
.
R-hyperCVAD/MA has a higher treatment-related mortality rate (11% vs 5%-8%), which may be due to the longer treatment time
.
The R-CODOX-M±IVAC regimen has a shorter treatment time, and can effectively cover the CNS even when the patient has brain parenchymal CNS disease, and allows outpatient administration with lower toxicity
.
The efficacy of the low-intensity DA-EPOCH-R regimen has been verified in a multi-center, phase II clinical trial
.
The 5-year EFS rate of the low-intensity DA-EPOCH-R regimen in this study was 85%
.
It is worth noting that the low-risk BL patients in the study did not receive preventive treatment for the CNS, and the EFS rate reached 100% after 3 treatment cycles.
There are still many unmet clinical needs in patients with relapsed and refractory BL.
The overall prognosis of this part of patients is poor, and there is a lack of disease-specific data
.
Most patients with BL have a rapid recurrence and usually involve the CNS.
Some patients with relapsed and refractory BL may be sensitive to salvage chemotherapy
.
The efficacy of chimeric antigen receptor T cell (CAR-T) immunotherapy, antibody-drug conjugates, bispecific antibodies, and related targeted drugs in patients with relapse and refractory remains to be verified
.
Summary The current prognostic model of BL relies on clinical indicators related to disease burden, and its accuracy is limited
.
It is necessary to further optimize the BL prognosis model, and to further determine the factors related to disease recurrence through related studies
.
Low-risk BL can be cured by the simplified DA-EPOCH-R regimen
.
The efficacy of DA-EPOCH-R program combined with related targeted drugs in high-risk BL patients needs to be further explored through research
.
Reference source: 1.
Adam J Olszewski, et al.
2021 SOHO.
EXABS-108-NHL.
Stamp "read the original text", we make progress together
