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American Journal of Hematology Dec 2022Follicular lymphoma (FL) is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. FL is characterized by diffuse...
DISEASE OVERVIEW
Follicular lymphoma (FL) is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. FL is characterized by diffuse lymphadenopathy, bone marrow involvement, and splenomegaly. Extranodal involvement is less common. Cytopenias are relatively common but constitutional symptoms of fever, night sweats, and weight loss are uncommon in the absence of transformation to diffuse large B cell lymphoma.
DIAGNOSIS
The diagnosis is based on histology from a biopsy of a lymph node or other affected tissue. Incisional biopsy is preferred over needle biopsies in order to give adequate tissue to assign grade and assess for transformation. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10, and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes.
RISK STRATIFICATION
The Follicular Lymphoma International Prognostic Index (FLIPI) uses five independent predictors of inferior survival: age >60 years, hemoglobin <12 g/dL, serum LDH > normal, Ann Arbor stage III/IV, number of involved nodal areas >4. The presence of 0-1, 2, and ≥3 adverse factors defines low, intermediate, and high-risk disease. There are other clinical prognostic models but the FLIPI remains the most common. Other factors such as time to relapse of less than 2 years from chemoimmunotherapy and specific gene mutations may also be useful for prognosis. Regardless of the prognostic model used, modern therapies have demonstrably improved prognosis.
RISK-ADAPTED THERAPY
Observation continues to be appropriate for asymptomatic patients with low bulk disease and no cytopenias. There is no overall survival (OS) advantage for early treatment with either chemotherapy or single-agent rituximab. For patients needing therapy, most patients are treated with chemoimmunotherapy, which has improved overall response rates (ORR), DOR, and OS. Randomized studies have shown additional benefits for maintenance of rituximab. Lenalidomide was non-inferior to chemoimmunotherapy in a randomized front-line study and, when combined with rituximab, was superior to rituximab alone in relapsed FL. Kinase inhibitors, stem cell transplantation (SCT), and chimeric antigen receptor T cells (CAR-T) are also considered for recurrent disease.
Topics: Humans; Middle Aged; Lymphoma, Follicular; Rituximab; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Prognosis
PubMed: 36255040
DOI: 10.1002/ajh.26737 -
American Journal of Hematology Mar 2020Follicular lymphoma (FL) is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma is characterized by... (Review)
Review
DISEASE OVERVIEW
Follicular lymphoma (FL) is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma is characterized by diffuse lymphadenopathy, bone marrow involvement, and splenomegaly. Extranodal involvement is less common. Cytopenias are relatively common but constitutional symptoms of fever, night sweats, and weight loss are uncommon in the absence of transformation to diffuse large B cell lymphoma.
DIAGNOSIS
The diagnosis is based on histology from a biopsy of a lymph node or other affected tissue. Incisional biopsy is preferred over needle biopsies in order to give adequate tissue to assign grade and assess for transformation. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10 and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes.
RISK STRATIFICATION
The Follicular Lymphoma International Prognostic Index (FLIPI) uses five independent predictors of inferior survival: age > 60 years, hemoglobin <12 g/dL, serum LDH > normal, Ann Arbor stage III/IV, number of involved nodal areas >4. The presence of 0-1, 2, and ≥ 3 adverse factors defines low, intermediate, and high-risk disease. There are other clinical prognostic models but the FLIPI remains the most common. Other factors such as time to relapse of less than 2 years from chemoimmunotherapy and specific gene mutations may also be useful for prognosis. Regardless of the prognostic model used, modern therapies have demonstrably improved prognosis.
RISK-ADAPTED THERAPY
Observation continues to be appropriate for asymptomatic patients with low bulk disease and no cytopenias. There is no overall survival advantage for early treatment with either chemotherapy or single agent rituximab. For patients needing therapy, most patients are treated with chemoimmunotherapy, which has improved response rates, duration of response and overall survival (OS). Randomized studies have shown additional benefit for maintenance rituximab. Lenalidomide was non-inferior to chemoimmunotherapy in a randomized front-line study and, when combined with rituximab, was superior to rituximab alone in relapsed FL. Kinase inhibitors, other immunotherapies, and stem cell transplantation (SCT) are also considered for recurrent disease.
Topics: Biomarkers, Tumor; Humans; Lymphoma, Follicular; Neoplasm Proteins; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 31814159
DOI: 10.1002/ajh.25696 -
Virchows Archiv : An International... Jan 2023Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent mature B-cell neoplasms with variable clinical presentation and distinct histopathologic features.... (Review)
Review
Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent mature B-cell neoplasms with variable clinical presentation and distinct histopathologic features. Recent advances in the biology and molecular characteristics of these lymphomas have further expanded our understanding of the heterogeneous nature of these lymphomas, with increasing recognition of specific disease entities within the broader categories of FL and MZL. Here, we discuss the conclusions of the 2022 International Consensus Classification of Mature Lymphoid Neoplasms (2022 ICC) dealing with FL, and review differences with the proposed WHO 5th Edition classification. We review issues related to grading and alternative forms of FL especially those lacking the genetic hallmark of FL, the t(14;18) chromosomal alteration. Among them, t(14;18)-negative CD23 follicle center lymphoma has been proposed by the 2022 ICC as a provisional entity. Other follicle center-derived lymphomas such as pediatric-type follicular lymphoma, testicular follicular lymphoma, primary cutaneous follicle center lymphoma, and large B-cell lymphoma with IRF4 rearrangement are considered distinct entities separate from conventional FL. Importantly, large B-cell lymphoma with IRF4 rearrangement introduced as a provisional entity in the WHO 2017 is upgraded to a definite entity in the 2022 ICC. We also discuss diagnostic strategies for recognition of MZLs including splenic MZL, extranodal MZL (MALT lymphoma), and primary nodal MZL. The importance of molecular studies in the distinction among marginal zone lymphoma subtypes is emphasized, as well as their value in the differential diagnosis with other B-cell lymphomas.
Topics: Child; Humans; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Interferon Regulatory Factors; Lymphoma, Large B-Cell, Diffuse
PubMed: 36394631
DOI: 10.1007/s00428-022-03432-2 -
Hematology/oncology Clinics of North... Aug 2020Follicular lymphoma (FL) is a common indolent lymphoma subtype in Western countries. FL incidence increases with age, and shows considerable variation by race/ethnicity... (Review)
Review
Follicular lymphoma (FL) is a common indolent lymphoma subtype in Western countries. FL incidence increases with age, and shows considerable variation by race/ethnicity and geography. In the United States and France, FL incidence has been stable since 2000, whereas in other Western and Asian countries it has been increasing. Five-year relative survival rates have been increasing in Western and Asian countries. Progress on identifying FL-specific risk factors has accelerated with the implementation of the InterLymph nested classification and the availability of larger epidemiologic studies and pooled analyses. Identification of risk factors for FL requires further research.
Topics: Age Distribution; Combined Modality Therapy; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Incidence; Lymphoma, Follicular; Risk Assessment; Risk Factors; SEER Program; Survival Rate; Treatment Outcome; United States
PubMed: 32586570
DOI: 10.1016/j.hoc.2020.02.001 -
Annals of Hematology Jan 2018Follicular Lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and is considered to be the prototype of indolent lymphomas. Histologic transformation... (Review)
Review
Follicular Lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and is considered to be the prototype of indolent lymphomas. Histologic transformation into an aggressive lymphoma, which is expected to occur at a rate of 2 to 3% each year, is associated with rapid progression, treatment resistance, and poor prognosis. Recent modifications to the physiopathologic mechanism of transformed follicular lymphoma (t-FL) have been proposed, including genetic and epigenetic mechanisms as well as a role for the microenvironment. Although t-FL is considered a devastating complication, as it is associated with treatment-refractory disease and a dismal outcome, recent data in the rituximab era have suggested that not only is the prognosis less severe than reported in the previous literature but the risk of transformation is also lower. Thus, this study aimed to review the most recent research on t-FL in an attempt to better understand the clinical meaning of transformation from FL to diffuse large B cell lymphoma (DLBCL) and the impact of current treatment strategies on the curability of this intriguing subentity of lymphoma.
Topics: Cell Transformation, Neoplastic; Disease Progression; Humans; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 29043381
DOI: 10.1007/s00277-017-3151-2 -
Annals of Oncology : Official Journal... Mar 2021
Topics: Antineoplastic Combined Chemotherapy Protocols; Follow-Up Studies; Health Planning Guidelines; Humans; Lymphoma, Follicular; Neoplasm Recurrence, Local; Neoplasm Staging; Rituximab
PubMed: 33249059
DOI: 10.1016/j.annonc.2020.11.008 -
Blood Cancer Journal Jul 2020Patients with follicular lymphoma (FL) frequently require multiple treatments during their disease course; however, survival based on lines of treatment remains poorly...
Patients with follicular lymphoma (FL) frequently require multiple treatments during their disease course; however, survival based on lines of treatment remains poorly described in the post-rituximab era. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score was developed to predict survival at diagnosis, yet it remains unknown whether increase in FLIPI score following an initial observation period is associated with less-favorable outcomes. To address these knowledge gaps, we retrospectively studied 1088 patients with FL grade 1-3A managed between 1998 and 2009 at our institution. Median overall survival (OS) and progression-free survival (PFS) after first-line treatment were not reached and 4.73 years, respectively. Following successive lines of treatment, years of median OS and PFS were, respectively: after second-line, 11.7 and 1.5; third-line, 8.8 and 1.1; fourth-line, 5.3 and 0.9; fifth-line, 3.1 and 0.6; sixth-line, 1.9 and 0.5. In initially observed, subsequently treated patients, FLIPI score increase after observation was associated with inferior survival following first-line treatment. The reduced survival we observed after second-line and later therapy supports the development of new treatments for relapsed patients and benchmarks historical targets for clinical endpoints. This study also highlights the utility of changes in FLIPI score at diagnosis and after observation in identifying patients likely to have worse outcomes.
Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Disease Management; Female; Follow-Up Studies; Humans; Lymphoma, Follicular; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Public Health Surveillance; Retrospective Studies; Risk Assessment; Risk Factors; Survival Analysis; Survival Rate; Treatment Outcome; Young Adult
PubMed: 32678074
DOI: 10.1038/s41408-020-00340-z -
Blood Apr 2022
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Lymphoma, Follicular
PubMed: 35420687
DOI: 10.1182/blood.2021015120 -
The Lancet. Haematology Apr 2022Novel therapies for relapsed or refractory follicular lymphoma are commonly evaluated in single-arm studies without formal comparison with other treatments or historical...
Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study.
BACKGROUND
Novel therapies for relapsed or refractory follicular lymphoma are commonly evaluated in single-arm studies without formal comparison with other treatments or historical controls. Consequently, rigorously defined treatment outcomes informing expectations for novel therapeutic strategies in this population are sparse. To inform outcome expectations, we aimed to describe treatment patterns, survival outcomes, and duration of response in patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy.
METHODS
In this multicentre cohort study, we developed a database of patients with relapsed or refractory follicular lymphoma from eight academic centres in the USA using data collected in the LEO Cohort study (NCT02736357) and the LEO Consortium. For this analysis, eligible patients were aged at least 18 years, had non-transformed grade 1-3a follicular lymphoma, and were receiving systemic therapy in the third line or later after previous therapy with an anti-CD20 antibody and an alkylating agent. Clinical data and patient outcomes were abstracted from medical records by use of a standard protocol. The index therapy for the primary analysis was defined as the first line of systemic therapy after the patient had received at least two previous systemic therapies that included an alkylating agent and an anti-CD20 therapy. The main endpoints of interest were overall response rate, progression-free survival, and overall survival. Outcomes were also evaluated in subsets of clinical interest (index therapy characteristics, patient and disease characteristics, treatment history, and best response assessment).
FINDINGS
We screened 933 patients with follicular lymphoma, of whom 441 were included and diagnosed between March 6, 2002, and July 20, 2018. Index therapies included immunochemotherapy (n=133), anti-CD20 antibody monotherapy (n=53), lenalidomide with or without anti-CD20 (n=37), and phosphoinositide 3-kinase inhibitors with or without anti-CD20 (n=25). 57 (13%) of 441 patients received haematopoietic stem-cell transplantation and 98 (23%) of 421 patients with complete data received therapy on clinical trials. After a median follow-up of 71 months (IQR 64-79) from index therapy, 5-year overall survival was 75% (95% CI 70-79), median progression-free survival was 17 months (15-19), and the overall response rate was 70% (65-74; 280 of 400 patients evaluable for response). Patients who were refractory to therapy with an alkylating agent had a lower overall response rate (170 [68%] of 251 patients vs 107 [77%] of 139 patients) and a significantly lower 5-year overall survival (72%, 95% CI 66-78 vs 81%, 73-89; hazard ratio 1·60, 95% CI 1·04-2·46) than patients who were not refractory to therapy with an alkylating agent.
INTERPRETATION
Patients with relapsed or refractory follicular lymphoma receive heterogeneous treatments in the third-line setting or later. We observed high response rates to contemporary therapies that were of short duration. These data identify unmet needs among patients with follicular lymphoma, especially those who are refractory to alkylating agents, and might provide evidence by which clinical trials evaluating novel treatments could be assessed.
FUNDING
Genentech and the National Cancer Institute.
Topics: Adolescent; Adult; Antigens, CD20; Cohort Studies; Humans; Lymphoma, Follicular; Neoplasm Recurrence, Local; Phosphatidylinositol 3-Kinases
PubMed: 35358443
DOI: 10.1016/S2352-3026(22)00033-3 -
Journal of Cancer Research and... 2021Follicular T-cell lymphoma is a recently described, rare neoplasm with the true incidence still unknown. It is a lymph node-based tumor in which the node shows a...
Follicular T-cell lymphoma is a recently described, rare neoplasm with the true incidence still unknown. It is a lymph node-based tumor in which the node shows a follicular pattern of growth. Immunohistochemistry confirms the cells of origin to be follicular helper T-cells and thus plays an important role in the diagnosis of the tumor. We report a case of follicular variant of peripheral T-cell lymphoma, which was erroneously reported as Hodgkin lymphoma on fine-needle aspiration, and follicular lymphoma on hematoxylin and eosin.
Topics: Antineoplastic Agents, Alkylating; Biomarkers, Tumor; Biopsy, Fine-Needle; Diagnostic Errors; Hodgkin Disease; Humans; Lymph Nodes; Lymphoma, Follicular; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Treatment Outcome
PubMed: 34916399
DOI: 10.4103/jcrt.JCRT_486_19