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Author: Chunlan Qiugui This article is authorized by the author to publish by Yimaitong, please do not reprint without authorization.
Follicular lymphoma (FL) is the second most common lymphoma subtype, and the incidence has been on the rise in recent years.
In daily clinical practice, accurate diagnosis, staging and prognostic stratification of FL is conducive to individualized diagnosis and treatment and improve the overall efficacy of FL patients.
This article aims to sort out the diagnosis, staging and prognostic stratification criteria of FL, and on this basis summarize the research progress of the treatment of newly diagnosed FL.
Diagnosis of FL The histopathological diagnosis of FL should be based on surgery/resection of lymph nodes (LN), and lymph node biopsy is only used when the patient does not have an easily accessible LN (such as retroperitoneum).
It should be noted that FL may be heterogeneous, and it may be difficult to determine its histological grade in a needle biopsy.
If the pathological tissue is insufficient, another biopsy may be required.
The use of fine needle aspiration for preliminary diagnosis is not recommended.
The histological grade of FL is based on the average number of central blasts/high power field.
FL classified as 3B (with a sheet of central blast) is different from the indolent types classified as 1, 2 and 3A, and is considered aggressive lymphoma, which should be treated as aggressive lymphoma.
The pathological examination of FL should be performed by a professional hematologist, especially when distinguishing 3A and 3B grades.
FL staging FL staging has a greater influence in formulating treatment strategies, so accurate staging before treatment is particularly important.
The initial FL examination should include bone marrow smears and biopsy, as well as (neck + chest + abdomen) CT scan.
In addition, because PET-CT can improve the accuracy of staging, it is currently recommended for the routine staging of FL.
The current FL staging program is based on the Ann Arbor staging system revised at the Lugano meeting in 2014 (see Table 1 for details); according to this staging system, early (stage I and II) FL patients account for 10%-15%.
Table 1 The prognostic stratification of FL in the Ann Arbor staging system revised at the Lugano meeting in 2014.
In order to better stratify the prognosis of FL, the FL prognostic index (FLIPI) was established.
For patients in need of treatment, it is recommended to use the revised FLIPI 2 And simplified PRIMA FLIPI (see Table 2 for details).
Recently, based on the FLIPI score and the mutation status of 7 genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), a new clinical risk scoring system (m7-FLIPI) has been proposed, but it has not been used in routine clinical practice.
Table 2 FL prognostic stratification system: FLIPI and PRIMA FLIPI first-diagnosed limited-stage FL treatment For limited-stage (I and II) FL with low tumor burden, the preferred treatment strategy based on radiotherapy (RT) or ISRT (24-30Gy) .
The combination of RT and rituximab combined with chemotherapy (ChT) improved the patient's progression-free survival (PFS) compared to RT alone.
For patients with high tumor burden, poor clinical prognosis, and limited-stage FL patients who are not suitable for ISRT, systemic treatment should be performed according to advanced FL.
Treatment of newly diagnosed advanced FL 01 induction therapy is currently incurable for newly diagnosed advanced FL.
Previous studies have shown that [1], in the pre-rituximab era, initiation of treatment in asymptomatic advanced FL patients does not improve the overall survival (OS) of the patients.
A recent study showed that the use of rituximab to treat asymptomatic advanced FL can improve PFS in patients, but so far there is no evidence of OS benefit [2].
Therefore, at present, patients with advanced FL who have no indications for treatment choose to observe and wait, and only start treatment for patients with indications for treatment.
See Table 3 for specific treatment indications.
Table 3 FL treatment indications have been confirmed by studies [3-4].
In patients with advanced FL with treatment indications, rituximab combined with ChT can significantly improve the overall response rate (ORR) of patients compared with ChT alone.
), PFS and OS.
In addition, studies have shown [5] that R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) or BR ( Compared with R-CVP (rituximab, vincristine and prednisone) regimen treatment, rituximab and bendamustine can make patients have a higher complete remission (CR) rate and Longer PFS, but similar OS.
The results of a randomized clinical study of newly diagnosed patients with advanced FL with indications for treatment showed that [6], in the use of immunochemotherapy and up to 2 years of maintenance therapy, the new CD20 monoclonal antibody otuzumab was used ( Obinutuzumab) significantly improved patients' PFS compared with rituximab.
Although no benefit from OS was observed, it is currently considered to be a more effective treatment option.
The results of another international multi-center, phase III clinical study [7] showed that lenalidomide combined with rituximab (R2) has a similar efficacy to immunochemotherapy in patients with advanced FL with indications for treatment.
02 Consolidation/maintenance treatment Progressive FL is treated with rituximab once every 2 months for 2 years after induction treatment with various schemes, which can significantly improve the PFS of patients, but not OS [8].
In the era before rituximab treatment, autologous hematopoietic stem cell transplantation (ASCT) consolidation therapy after ChT can prolong PFS in patients, but the advantages of ASCT after induction therapy with rituximab-containing immunochemotherapy regimen are lost [9].
Therefore, ASCT is not currently recommended for the consolidation treatment of newly diagnosed advanced FL patients.
References: [1].
Bachy E, Maurer MJ, Habermann TM, et al.
A simplified scoring system in de novofollicular lymphoma treated initially with immunochemotherapy.
Blood.
2018;132(1):49-58.
[2].
Ardeshna KM, Qian W, Smith P, et al.
Rituximab versus a watch-andwait approach in patients with advanced-stage,asymptomatic, nonbulky follicular lymphoma: an open-label randomised phase 3trial.
Lancet Oncol.
2014;15:424-435.
[3].
Marcus R,Imrie K, Solal-Céligny P, et al.
Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisolone alone in patients withpreviously untreated advanced follicular lymphoma.
J Clin Oncol.
2008;26:4579 -4586.
[4].
Hiddemann W,Kneba M, Dreyling M, et al.
Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine,and prednisone(CHOP) significantly improves the outcome of patients with advanced stagefollicular lymphoma compared with therapy with CHOP alone: results of aprospective randomized study of the German Low Grade Lymphoma StudyGroup.
Blood.
2005;106:3725-3732.
[5].
Luminari S,Ferrari A, Manni M, et al.
Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma.
J Clin Oncol.
2018;36 (7):689-696.
[6].
Marcus R,Davies A, Ando K, et al.
Obinutuzumab for the first-line treatment offollicular lymphoma.
N Engl J Med.
2017;377(14):1331-1344.
[7].
MorschhauserF, Fowler NH, Feugier P, et al.
Rituximab plus lenalidomide in advanceduntreated follicular lymphoma.
N Engl J Med.
2018;379:934-947.
[8].
Bachy E, Seymour JF, Feugier P, et al.
Sustained progression-free survival benefit ofrituximab maintenance in patients with follicular lymphoma: long-term resultsof the PRIMA study.
J Clin Oncol.
2019;37(31):2815-2824.
[9].
Schaaf M,Reiser M, Borchmann P, et al.
High-dose therapy with autologous stem celltransplantation versus chemotherapy or immunochemotherapy for follicularlymphoma in adults.
Cochrane Database yst Rev.
2012;1:CD007678.
Click "Read the original text" and we will make progress together
Follicular lymphoma (FL) is the second most common lymphoma subtype, and the incidence has been on the rise in recent years.
In daily clinical practice, accurate diagnosis, staging and prognostic stratification of FL is conducive to individualized diagnosis and treatment and improve the overall efficacy of FL patients.
This article aims to sort out the diagnosis, staging and prognostic stratification criteria of FL, and on this basis summarize the research progress of the treatment of newly diagnosed FL.
Diagnosis of FL The histopathological diagnosis of FL should be based on surgery/resection of lymph nodes (LN), and lymph node biopsy is only used when the patient does not have an easily accessible LN (such as retroperitoneum).
It should be noted that FL may be heterogeneous, and it may be difficult to determine its histological grade in a needle biopsy.
If the pathological tissue is insufficient, another biopsy may be required.
The use of fine needle aspiration for preliminary diagnosis is not recommended.
The histological grade of FL is based on the average number of central blasts/high power field.
FL classified as 3B (with a sheet of central blast) is different from the indolent types classified as 1, 2 and 3A, and is considered aggressive lymphoma, which should be treated as aggressive lymphoma.
The pathological examination of FL should be performed by a professional hematologist, especially when distinguishing 3A and 3B grades.
FL staging FL staging has a greater influence in formulating treatment strategies, so accurate staging before treatment is particularly important.
The initial FL examination should include bone marrow smears and biopsy, as well as (neck + chest + abdomen) CT scan.
In addition, because PET-CT can improve the accuracy of staging, it is currently recommended for the routine staging of FL.
The current FL staging program is based on the Ann Arbor staging system revised at the Lugano meeting in 2014 (see Table 1 for details); according to this staging system, early (stage I and II) FL patients account for 10%-15%.
Table 1 The prognostic stratification of FL in the Ann Arbor staging system revised at the Lugano meeting in 2014.
In order to better stratify the prognosis of FL, the FL prognostic index (FLIPI) was established.
For patients in need of treatment, it is recommended to use the revised FLIPI 2 And simplified PRIMA FLIPI (see Table 2 for details).
Recently, based on the FLIPI score and the mutation status of 7 genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), a new clinical risk scoring system (m7-FLIPI) has been proposed, but it has not been used in routine clinical practice.
Table 2 FL prognostic stratification system: FLIPI and PRIMA FLIPI first-diagnosed limited-stage FL treatment For limited-stage (I and II) FL with low tumor burden, the preferred treatment strategy based on radiotherapy (RT) or ISRT (24-30Gy) .
The combination of RT and rituximab combined with chemotherapy (ChT) improved the patient's progression-free survival (PFS) compared to RT alone.
For patients with high tumor burden, poor clinical prognosis, and limited-stage FL patients who are not suitable for ISRT, systemic treatment should be performed according to advanced FL.
Treatment of newly diagnosed advanced FL 01 induction therapy is currently incurable for newly diagnosed advanced FL.
Previous studies have shown that [1], in the pre-rituximab era, initiation of treatment in asymptomatic advanced FL patients does not improve the overall survival (OS) of the patients.
A recent study showed that the use of rituximab to treat asymptomatic advanced FL can improve PFS in patients, but so far there is no evidence of OS benefit [2].
Therefore, at present, patients with advanced FL who have no indications for treatment choose to observe and wait, and only start treatment for patients with indications for treatment.
See Table 3 for specific treatment indications.
Table 3 FL treatment indications have been confirmed by studies [3-4].
In patients with advanced FL with treatment indications, rituximab combined with ChT can significantly improve the overall response rate (ORR) of patients compared with ChT alone.
), PFS and OS.
In addition, studies have shown [5] that R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) or BR ( Compared with R-CVP (rituximab, vincristine and prednisone) regimen treatment, rituximab and bendamustine can make patients have a higher complete remission (CR) rate and Longer PFS, but similar OS.
The results of a randomized clinical study of newly diagnosed patients with advanced FL with indications for treatment showed that [6], in the use of immunochemotherapy and up to 2 years of maintenance therapy, the new CD20 monoclonal antibody otuzumab was used ( Obinutuzumab) significantly improved patients' PFS compared with rituximab.
Although no benefit from OS was observed, it is currently considered to be a more effective treatment option.
The results of another international multi-center, phase III clinical study [7] showed that lenalidomide combined with rituximab (R2) has a similar efficacy to immunochemotherapy in patients with advanced FL with indications for treatment.
02 Consolidation/maintenance treatment Progressive FL is treated with rituximab once every 2 months for 2 years after induction treatment with various schemes, which can significantly improve the PFS of patients, but not OS [8].
In the era before rituximab treatment, autologous hematopoietic stem cell transplantation (ASCT) consolidation therapy after ChT can prolong PFS in patients, but the advantages of ASCT after induction therapy with rituximab-containing immunochemotherapy regimen are lost [9].
Therefore, ASCT is not currently recommended for the consolidation treatment of newly diagnosed advanced FL patients.
References: [1].
Bachy E, Maurer MJ, Habermann TM, et al.
A simplified scoring system in de novofollicular lymphoma treated initially with immunochemotherapy.
Blood.
2018;132(1):49-58.
[2].
Ardeshna KM, Qian W, Smith P, et al.
Rituximab versus a watch-andwait approach in patients with advanced-stage,asymptomatic, nonbulky follicular lymphoma: an open-label randomised phase 3trial.
Lancet Oncol.
2014;15:424-435.
[3].
Marcus R,Imrie K, Solal-Céligny P, et al.
Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisolone alone in patients withpreviously untreated advanced follicular lymphoma.
J Clin Oncol.
2008;26:4579 -4586.
[4].
Hiddemann W,Kneba M, Dreyling M, et al.
Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine,and prednisone(CHOP) significantly improves the outcome of patients with advanced stagefollicular lymphoma compared with therapy with CHOP alone: results of aprospective randomized study of the German Low Grade Lymphoma StudyGroup.
Blood.
2005;106:3725-3732.
[5].
Luminari S,Ferrari A, Manni M, et al.
Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma.
J Clin Oncol.
2018;36 (7):689-696.
[6].
Marcus R,Davies A, Ando K, et al.
Obinutuzumab for the first-line treatment offollicular lymphoma.
N Engl J Med.
2017;377(14):1331-1344.
[7].
MorschhauserF, Fowler NH, Feugier P, et al.
Rituximab plus lenalidomide in advanceduntreated follicular lymphoma.
N Engl J Med.
2018;379:934-947.
[8].
Bachy E, Seymour JF, Feugier P, et al.
Sustained progression-free survival benefit ofrituximab maintenance in patients with follicular lymphoma: long-term resultsof the PRIMA study.
J Clin Oncol.
2019;37(31):2815-2824.
[9].
Schaaf M,Reiser M, Borchmann P, et al.
High-dose therapy with autologous stem celltransplantation versus chemotherapy or immunochemotherapy for follicularlymphoma in adults.
Cochrane Database yst Rev.
2012;1:CD007678.
Click "Read the original text" and we will make progress together
