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1.
Rinsho Ketsueki ; 60(9): 1199-1204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597844

RESUMO

The treatment of follicular lymphoma (FL) continues to evolve. Those patients who present with minimal symptoms often are observed without therapy until significant progression occurs. When treatment is needed, initial options include single agent rituximab (R, anti-CD20), or various forms of chemoimmunotherapy including either R or the newer anti-CD20 monoclonal antibody obinutuzumab (O), with or without maintenance administration. Recent data suggest that the immunomodulatory agent lenalidomide can also be effective in combination with rituximab in both the upfront and relapsed setting. Patients with recurrent disease are frequently treated with chemoimmunotherapy or phosphoinositol-3-kinase (PI3K) inhibitors. Current information suggests that the most important prognostic feature of FL is the presence or absence of early progression (within 2 years of initial treatment/diagnosis). Ongoing efforts are focused on biomarkers to optimally match treatment to patient populations and further improve clinical outcomes.


Assuntos
Linfoma Folicular/terapia , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD20 , Humanos , Imunoterapia , Lenalidomida/uso terapêutico , Rituximab/uso terapêutico
2.
Presse Med ; 48(7-8 Pt 1): 850-858, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447334

RESUMO

Follicular lymphoma, the second most common lymphoma, is characterized by its slow growth and is often considered incurable in advanced stages. Progresses in biology have contributed to better understand the complex and successive mechanisms of development of this pathology, whose diagnosis is based on a lymph node biopsy. However, the prognosis of the patients is heterogeneous and several indexes have been proposed to identify groups of patients with a similar life expectancy, in order to guide the therapeutic choices. The treatment has been modified in the last 20 years by the emergence of anti-CD20 monoclonal antibodies which constitute, alone or in combination, of the cornerstone of therapeutic management. After staging using, in particular, 18-fluorodeoxyglucose positron emission tomography, the therapeutic strategy will be adapted for each patient, ranging from simple watchful waiting to a combination of chemotherapy and anti-CD20 antibodies. Relapses (which often require a new lymph node biopsy to eliminate a possible histological transformation into an aggressive lymphoma with poorer prognosis) remain common but are still accessible to effective therapeutic interventions. Thanks to these advances, the median life expectancy of patients with follicular lymphoma now exceeds 15 years.


Assuntos
Linfoma Folicular , Biópsia , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia/métodos , Imunoterapia/tendências , Expectativa de Vida , Linfoma Folicular/diagnóstico , Linfoma Folicular/epidemiologia , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Técnicas de Diagnóstico Molecular , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Prognóstico , Taxa de Sobrevida , Terapias em Estudo/métodos , Terapias em Estudo/tendências
3.
Hematol Oncol ; 37 Suppl 1: 53-61, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187530

RESUMO

Pediatric-type follicular lymphoma (PTFL), pediatric nodal marginal zone lymphoma (pnMZL), and large B-cell lymphoma (LBCL) with IRF4 rearrangement have been introduced into the current World Health Organization (WHO) classification. They account for 5% to 10% of mature B-cell lymphomas in children and adolescents. Both PTFL and pnMZL predominantly affect male adolescents and usually present with localized lymphadenopathy in the head and neck region. The cells within the follicles of PTFL typically show high-grade cytology, IGH monoclonality and lack the t(14;18) chromosomal alteration. In contrast, pnMZL is characterized by progressive transformation of germinal center (PTGC)-like features and interfollicular proliferation of the cells with expansion of the marginal zones with diffuse areas. Watch and wait after complete resection seems an adequate therapy with chemotherapy restricted to incompletely resected disease. All children with PTFL and pnMZL reported, so far, survived. B-cell lymphomas presenting in the Waldeyer's ring are characterized by the expression of IRF4/MUM1 and often associated with IRF4 rearrangements. Because of the frequent diffuse component, treatment often follows current protocols for mature B-NHL. The prognosis is excellent.


Assuntos
Linfoma de Células B/diagnóstico , Adolescente , Fatores Etários , Biópsia , Criança , Terapia Combinada , Humanos , Imuno-Histoquímica , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Linfoma de Células B/epidemiologia , Linfoma de Células B/etiologia , Linfoma de Células B/terapia , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma Folicular/diagnóstico , Linfoma Folicular/epidemiologia , Linfoma Folicular/terapia , Técnicas de Diagnóstico Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Resultado do Tratamento
5.
Blood Rev ; 35: 68-80, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30928169

RESUMO

Follicular lymphoma (FL) is the most common indolent lymphoma. Therapeutic advances in the past decade have improved its prognosis, but some questions remain open, particularly over adapting therapy to each individual patient's disease risk. Several trials and large studies dealing with biological and therapeutic aspects of FL have been published in the past few months and may have immediate or near-future practice-changing implications. These studies include risk-assessment by gene expression profiling, the therapeutic strategy in localized FL, use of obinutuzumab or lenalidomide in the front-line setting, stem cell transplant in early treatment failure and phosphatidylinositol 3-kinase (PI3K) inhibition and chimeric antigen receptor (CAR) T-cells in multiply relapsed disease. This review aims to contextualize these studies, summarize their design and results, assess their impact, highlight related questions that remain unanswered and, finally, provide a personal view as to how they change our approach to non-transformed FL.


Assuntos
Linfoma Folicular/diagnóstico , Linfoma Folicular/etiologia , Linfoma Folicular/terapia , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Terapia Combinada , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Folicular/mortalidade , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento
6.
Value Health ; 21(10): 1176-1185, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30314618

RESUMO

OBJECTIVES: To use real-world data to develop a flexible generic decision model to predict cost, life expectancy, and quality-adjusted life-years (QALYs) for follicular lymphoma (FL) in the general patient population. METHODS: All patients newly diagnosed with FL in the UK's population-based Haematological Malignancy Research Network (www.hmrn.org) between 2004 and 2011 were followed until 2015 (N = 740). Treatment pathways, QALYs, and costs were incorporated into a discrete event simulation to reflect patient heterogeneity, including age and disease management. Two scenario analyses, based on the latest National Institute for Health and Clinical Excellence (NICE) guidelines (rituximab induction therapy for newly diagnosed asymptomatic patients and rituximab maintenance therapy for patients between treatments), were conducted and their economic impacts were compared to current practice. RESULTS: Incidence-based analysis revealed expected average lifetime costs ranging from £6,165 [US$7,709] to £63,864 [US$79,862] per patient, and average life expectancy from 75 days to 17.56 years. Prevalence-based analysis estimated average annual treatment costs of £60-65 million [US$75-80 million], accounting for approximately 10% of the United Kingdom's annual National Health Service budget for hematological cancers as a whole. Assuming that treatment effects reported in trials are applicable to all patient groups, scenario analyses for two recent NICE guidelines demonstrated potential annual cost savings for the United Kingdom that ranged with uptake frequency from £0.6 million to £11 million [US$0.75-2.75 million]. CONCLUSIONS: Costs, survival, and QALYs associated with FL vary markedly with patient characteristics and disease management. Allowing the production of more realistic outcomes across the patient population as a whole, our model addresses this heterogeneity and is a useful tool with which to evaluate new technologies/treatments to support healthcare decision makers.


Assuntos
Análise Custo-Benefício/tendências , Técnicas de Apoio para a Decisão , Expectativa de Vida/tendências , Linfoma Folicular/economia , Vigilância da População , Anos de Vida Ajustados por Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício/métodos , Feminino , Previsões , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Estatística como Assunto/métodos , Estatística como Assunto/tendências , Reino Unido/epidemiologia
7.
Virchows Arch ; 473(4): 453-462, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29858685

RESUMO

Primary cutaneous follicle center lymphoma (PCFCL) is an indolent variant of follicular lymphoma (FL) with limited information available on the genetic background of the disease. The genetic hallmark of nodal FL, the t(14;18) translocation, affecting the BCL2 gene, is rare in PCFCL. Loss of 1p36, the most common secondary chromosomal abnormality in nodal FL, has been recently reported in 16.7% of PCFCL cases. In order to further characterize PCFCL, 21 cases were analyzed using interphase fluorescence in situ hybridization with BCL2 break apart and 1p36/1q25 dual color probes. Sanger sequencing was used to investigate TNFRSF14 and EZH2 mutations and immunohistochemistry to assess BCL2, EZH2 protein expressions.1p36 deletion occurred in 22% (5/21), BCL2 gene break in 10% (2/20) of the PCFCL cases. Mutations of the candidate tumor suppressor gene of the 1p36 region, TNFRSF14 mutations were detected in 4/17 (23.5%) cases with 2 cases presenting with concurrent 1p36 deletion. EZH2 hotspot mutations at Y641, A682, and A692 were not found. High EZH2 protein expression associated with a BCL2 negative phenotype was observed in 43% (9/21) of the cases. BCL2 gene break or 1p36 deletion did not impact the prognosis; however, they showed association with advanced stages at diagnosis (p = 0.016) and a tendency with shorter event free survival (p = 0.052).In conclusion, 1p36 deletion co-occurs with acquired TNFRSF14 mutations, suggesting a role of this tumor suppressor gene in the development of a subgroup of PCFCL. High EZH2 protein expression associated with BCL2 negative phenotype is common and might represent an ideal therapeutic target.


Assuntos
Biomarcadores Tumorais/genética , Deleção Cromossômica , Cromossomos Humanos Par 1 , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Linfoma Folicular/genética , Mutação , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Análise Mutacional de DNA , Intervalo Livre de Doença , Proteína Potenciadora do Homólogo 2 de Zeste/análise , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Folicular/química , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Estudos Retrospectivos , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
8.
J Cancer Res Clin Oncol ; 144(6): 1173-1183, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29623467

RESUMO

PURPOSE: In patients with follicular lymphoma, secondary transformation to aggressive lymphoma (tFL) implies a poor prognosis. In principle, allogeneic haematopoietic cell transplantation (allo-HCT) offers a chance of cure for tFL but is rarely practiced. Aim of this retrospective multicenter study was to define the actual significance of allo-HCT in treatment of tFL. METHODS: The database of the German Registry for Stem Cell Transplantation (DRST) was screened for patients who underwent allo-HCT for tFL 1998-2008. Confirmation of tFL-diagnosis by local and/or pathologists of the National NHL Board was mandatory for enrolment. Gaps in reported EBMT Minimum Essential Data datasets (MED-A) were filled by local DRST data managers. Relevant HCT outcome variables were evaluated by uni- and multivariate statistical analysis. RESULTS: Median age of enrolled 33 patients was 51 years with a post allo-HCT median follow-up of 7.1 years of surviving patients. At time of HCT 24/33 patients had chemosensitive disease. In 24/33 patients reduced intensity conditioning (RIC) was used. Estimated 1, 2, 5-year overall survival (OS) and event-free survival rates were 49/39/33, and 33/30/24%. Cumulative 100 days non-relapse mortality was 25%. Chemosensitive disease, RIC, and limited chronic GvHD were identified as independent prognostic factors for OS. CONCLUSIONS: Allo-HCT offers the chance of cure for tFL.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Adulto , Idoso , Transformação Celular Neoplásica , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Homólogo
9.
Rev. Soc. Bras. Clín. Méd ; 16(1): 64-69, 20180000.
Artigo em Português | LILACS | ID: biblio-885011

RESUMO

O linfoma folicular é um tipo de linfoma não Hodgkin de células B indolente. Apenas 30% dos pacientes apresentam doença em fase inicial ao diagnóstico. Os pacientes com estadiamento III-IV estão entre a maioria dos diagnósticos da doença e apresentam altas taxas de recaída ou refratariedade ao tratamento. O linfoma folicular recaído ou refratário permanece um desafio para a prática clínica. O transplante de células-tronco hematopoéticas autólogo vem sendo utilizado há muito tempo nesse perfil de pacientes, com altos índices de complicações como segunda neoplasia e curto período de remissão. O transplante de células-tronco hematopoéticas alogênico com regime de condicionamento mieloablativo apresenta resultados pouco aceitáveis, devido ao aumento da mortalidade relacionada ao tratamento sem benefícios em sobrevida global, da sobrevida livre de doença ou da taxa de recaída que sustentem tal indicação O transplante de células-tronco hematopoéticas alogênico com regime de condicionamento com intensidade reduzida parece ser uma alternativa promissora, inclusive como primeiro transplante. Alguns estudos comparando os resultados dos três tipos de transplantes em pacientes com linfoma folicular recaído ou refratário, com enfoque principal no transplante de células-tronco hematopoéticas alogênico de condicionamento com intensidade reduzida, são descritos neste artigo de revisão.(AU)


Follicular Lymphoma is a type of indolent B-cell non-Hodgkin´s lymphoma. Only 30% of the patients present with an early phase of the disease at diagnosis. Patients with stage III-IV are among the majority of the diagnoses of the disease, and these have high rates of relapse or refractoriness to treatment. Relapsed or refractory follicular lymphoma remains a challenge for clinical practice. Autologous hematopoietic stem cell transplantation has been used for a long time in this profile of patients, with high rates of complications, such as second neoplasia and short remission period. The allogenic hematopoietic stem cell transplantation with myeloablative conditioning regimen presents poorly acceptable results due to increased treatment-related mortality with no overall survival benefits, disease-free survival, or relapse rate to warrant it. Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimen seems to be a promising alternative, even as the first transplant. Some studies comparing the results of the three types of transplants in patients with relapsed or refractory follicular lymphoma , with a main focus on hematopoietic stem cell transplantation allogenic with reduced-intensity conditioning regimen, will be described in this review article.(AU)


Assuntos
Humanos , Masculino , Feminino , Antibióticos Antineoplásicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Transplante Autólogo/métodos
10.
Hematol Oncol ; 36(4): 617-623, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29602222

RESUMO

Follicular lymphoma (FL) generally has an indolent clinical course, but in some patients, a histological transformation (HT) into aggressive entities may take place and often lead to a poorer survival. The rituximab era has seen an improved outcome of FL, including those with HT. The current treatment strategies for transformed FL are based on immunochemotherapy for the cases with HT at the time of diagnosis or as the first event after watchful waiting. Patients transforming after prior treatment of FL usually benefit from autologous stem cell transplant. Unfortunately, early assessment of the transformation risk remains elusive. Recent studies delved the mechanisms of HT, showing that this is a complex process, resulting from a number of epigenetic and genetic lesions occurring in the tumour cell population as well as progressive changes in the tumour microenvironment. This novel knowledge has prompted clinical investigations on a variety of new therapeutic strategies.


Assuntos
Linfoma Folicular/patologia , Linfoma Folicular/terapia , Transformação Celular Neoplásica/patologia , Humanos , Microambiente Tumoral
12.
Lancet Haematol ; 5(3): e102-e108, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29396094

RESUMO

BACKGROUND: Despite an abundance of therapeutic options, advanced-stage follicular lymphoma remains incurable. Furthermore, the ideal sequence and absolute benefit of post-induction therapy is unclear. We designed SWOG S0801 to assess the efficacy and safety of consolidative radioimmunotherapy and sequential maintenance rituximab following chemoimmunotherapy. METHODS: For this single-arm, phase 2, multicentre study, we enrolled patients aged 18 years and older with a diagnosis of stage III, IV, or bulky stage II follicular lymphoma, grades 1, 2, or 3a, who had not received previous therapy, from from 20 institutions within the United States National Cancer Institute Clinical Trials Network. Patients were assigned to a 5-year treatment plan consisting of R-CHOP (rituximab plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2], and prednisone or prednisolone [100 mg]) every 21 days for up to six cycles, with rituximab 375 mg/m2 given on day 1 of cycles 1-4, followed by 131iodine tositumomab radioimmunotherapy and subsequent maintenance rituximab 375 mg/m2 within 12 weeks after the sixth cycle of R-CHOP, every 3 months for up to 4 years. The primary endpoint was 3-year progression-free survival in the intention-to-treat population. Efficacy and safety analyses were done in the intention-to-treat population and the per-protocol population. This trial was registered with ClinicalTrials.gov, number NCT00770224. FINDINGS: Between April 1, 2009, and Dec 15, 2010, we enrolled 84 evaluable patients, of whom 73 completed R-CHOP and radioimmunotherapy. Of 69 patients who registered to maintenance therapy, only 41 completed the 4-year rituximab maintenance treatment. Progression-free survival at 3 years was 90% (95% CI 82-95). The most common grade 3 or worse adverse events included neutropenia in 48 (57%) patients, leucopenia in 34 (40%) patients, thrombocytopenia in 17 (20%) patients, and febrile neutropenia in 14 (17%) patients. Nine patients had possible treatment-related deaths during the study from secondary or unknown causes (n=3), cirrhosis (n=1), cardiac arrest (n=1), and secondary malignancies (n=4). Secondary malignancies occurred in seven patients, including two sarcomas, two colorectal carcinomas, two acute myelogenous leukaemias, and one case of renal-cell carcinoma. INTERPRETATION: SWOG S0801 showed near universal responses following chemoimmunotherapy and radioimmunotherapy. However, most discontinuations occurred during maintenance therapy, suggesting that rituximab over a 4-year span is not feasible for many patients. Nonetheless, this sequential therapeutic strategy resulted in good overall outcomes for patients, including a low incidence of early disease progression. FUNDING: The National Cancer Institute and GlaxoSmithKline.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/terapia , Radioimunoterapia , Rituximab/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/patologia , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Quimioterapia de Indução , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidade , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Radioimunoterapia/métodos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
13.
J Gastroenterol Hepatol ; 33(8): 1461-1468, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29377265

RESUMO

BACKGROUND AND AIM: Few reports have demonstrated the effectiveness of treatments for intestinal follicular lymphoma (FL) because of the limited number of patients who undergo comprehensive small intestinal examinations. This study compared the efficacy of rituximab-combined chemotherapy in patients with asymptomatic and low tumor burden (LTB) intestinal FL, according to the criteria of the Groupe d'Etude des Lymphomes Folliculaires, with that of a "watch and wait" (W&W) approach. METHODS: The endoscopic examination for entire gastrointestinal tracts was performed in 29 Japanese patients with intestinal FL. These patients had CD21-positive follicular dendritic cells arranged in a duodenal pattern. In a prospective, two-center, open-label trial, this study evaluated the efficacy of rituximab-combined chemotherapy ([cyclophosphamide, doxorubicin, vincristine, and prednisone] or [cyclophosphamide, vincristine, and prednisone]) and prolonged treatment with rituximab (R-Chemo+prolongedR) in 14 patients and compared their outcomes with those of 15 patients managed with a W&W approach. RESULTS: Four patients managed with the W&W plan showed worsening macroscopic findings, lesion area enlargement, or clinical stage progression but stayed on this plan because they had LTB and experienced no changes in bowel function. In the R-Chemo+prolongedR group, all patients achieved complete remission; recurrence occurred in one patient, who was subsequently managed with the W&W plan because of LTB. There were no significant differences in progression-free survival between the two groups (P = 0.1045). Overall survival was 100% in both groups. CONCLUSIONS: The prognoses of patients with asymptomatic intestinal FL and LTB who were managed with a W&W strategy were comparable with those of patients receiving R-Chemo+prolongedR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Intestinais/terapia , Linfoma Folicular/terapia , Rituximab/administração & dosagem , Conduta Expectante , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Neoplasias Intestinais/patologia , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento , Carga Tumoral , Vincristina/administração & dosagem
15.
Br J Haematol ; 180(2): 217-223, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29230799

RESUMO

Given that there are currently no clear recommendations regarding therapeutic options for rituximab refractory/relapsed follicular lymphoma patients, this study aimed to describe the real-life management of patients with refractory follicular lymphoma after systemic rituximab-containing regimens (rFL), and rFL patient characteristics. In this retrospective, national, multicentre study, descriptive analyses were mainly performed according to rituximab-containing regimen at rFL diagnosis [rituximab monotherapy (R-MONO), rituximab + chemotherapy (R-COMBO), and ongoing rituximab maintenance (R-MAINTAIN)]. The 459 analysed patients experienced rituximab-refractoriness between October 2013 and September 2015: R-MONO: 58 (13%), R-COMBO: 197 (43%), R-MAINTAIN: 204 (44%). Post-refractoriness strategies were heterogeneous: idelalisib ± rituximab (22%), without anti-lymphoma treatment (21%), rituximab-chemotherapy (21%) and stem cell transplantation (18%). Rituximab was continued in combination in 41% of cases. Chosen strategies varied according to patient age (without anti-lymphoma treatment: 28% of patients if ≥65 years vs. 12% if <65 years old; stem-cell transplantation: 4% vs. 38%), treatment line at rFL, FL International Prognostic Index score and prior treatment. This French retrospective study, the first one conducted in a large cohort of rFL patients, showed that further strategies were highly heterogeneous, depending notably on patient characteristics and previous treatment. These data are the basis for a better understanding of rFL management and for the design of clinical trials in these patients.


Assuntos
Linfoma Folicular/terapia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tomada de Decisão Clínica , Terapia Combinada , Comorbidade , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Retratamento , Estudos Retrospectivos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Rituximab/uso terapêutico
17.
Ann Hematol ; 97(1): 17-29, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29043381

RESUMO

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.


Assuntos
Transformação Celular Neoplásica , Linfoma Folicular/patologia , Transformação Celular Neoplásica/genética , Progressão da Doença , Humanos , Linfoma Folicular/genética , Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia , Resultado do Tratamento
18.
Br J Haematol ; 180(1): 52-59, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29076139

RESUMO

Recent evidence has shown that immediate treatment with rituximab induction, with and without maintenance, substantially reduces the need for further treatment in patients with advanced asymptomatic follicular lymphoma. This analysis estimates the cost-effectiveness of immediate treatment approaches in comparison to a watch and wait approach from the perspective of the UK National Health Service. A Markov decision model was developed to estimate the cost-effectiveness of treatment strategies in patients with asymptomatic follicular lymphoma. The model was populated using effectiveness data from a systematic literature review with the key clinical data sourced from a randomised trial, in which the treatment strategies were compared. Costs were estimated using UK national sources. In comparison to watchful waiting, both rituximab strategies were found to be more effective and cost saving. In comparison to rituximab induction, the addition of rituximab maintenance marginally increased effectiveness but substantially increased costs, resulting in an incremental cost-effectiveness ratio (ICER) of £69 406 per quality-adjusted life year (QALY). In probabilistic sensitivity analysis, rituximab induction was found to have a 68% probability of being cost-effective at a threshold of £20 000 per QALY. In conclusion, active treatment with rituximab induction is a cost-effective strategy to adopt in patients with asymptomatic follicular lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças Assintomáticas , Análise Custo-Benefício , Linfoma Folicular/diagnóstico , Linfoma Folicular/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Qualidade de Vida , Tempo para o Tratamento , Resultado do Tratamento
19.
J Oncol Pract ; 13(12): 798-806, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29232542

RESUMO

Follicular lymphoma (FL) exhibits striking biologic and clinical heterogeneity. Patients with newly diagnosed asymptomatic or low-bulk disease may be observed or managed with immunotherapies alone. Chemoimmunotherapy is considered a standard treatment for patients with advanced, symptomatic disease. In patients with FL who achieve at least a partial remission after first-line chemoimmunotherapy, autologous (auto-) hematopoietic cell transplantation (HCT) consolidation is not recommended; however, most patients with FL experience disease relapse after frontline therapies, with the experience of therapy failure within 2 years of first-line treatments predicting poor survival. Despite remarkable efficacy, even in patients who experience failure with other therapies, auto-HCT and allogeneic (allo-) HCT remain underutilized in relapsed/refractory FL, even among healthy and younger patients. Early use of auto-HCT consolidation should be considered a standard therapy option for high-risk patients who experience early failure of chemoimmunotherapy (< 2 years). For patients with FL who experience failure of frontline therapies late (> 2 years), deferring auto-HCT until later in the disease course is reasonable. Allo-HCT is best reserved for medically fit individuals with heavily pretreated disease, persistent marrow involvement, refractory, but low-bulk, disease, and in those who experience a failure to mobilize stem cells for auto-HCT. Allo-HCT is also a reasonable option for patients with FL who experience failure with a prior autograft; lower-intensity conditioning regimens and HLA-matched related donors are preferred in that setting. Future research should focus on the eradication of minimal residual disease before HCT and the prevention of disease relapse after HCT by integrating novel targeted agents into pre-HCT and post-HCT regimens.


Assuntos
Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoterapia/métodos , Linfoma Folicular/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Transplante Homólogo/métodos , Resultado do Tratamento
20.
N Engl J Med ; 377(26): 2545-2554, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29226764

RESUMO

BACKGROUND: Patients with diffuse large B-cell lymphoma or follicular lymphoma that is refractory to or that relapses after immunochemotherapy and transplantation have a poor prognosis. High response rates have been reported with the use of T cells modified by chimeric antigen receptor (CAR) that target CD19 in B-cell cancers, although data regarding B-cell lymphomas are limited. METHODS: We used autologous T cells that express a CD19-directed CAR (CTL019) to treat patients with diffuse large B-cell lymphoma or follicular lymphoma that had relapsed or was refractory to previous treatments. Patients were monitored for response to treatment, toxic effects, the expansion and persistence of CTL019 cells in vivo, and immune recovery. RESULTS: A total of 28 adult patients with lymphoma received CTL019 cells, and 18 of 28 had a response (64%; 95% confidence interval [CI], 44 to 81). Complete remission occurred in 6 of 14 patients with diffuse large B-cell lymphoma (43%; 95% CI, 18 to 71) and 10 of 14 patients with follicular lymphoma (71%; 95% CI, 42 to 92). CTL019 cells proliferated in vivo and were detectable in the blood and bone marrow of patients who had a response and patients who did not have a response. Sustained remissions were achieved, and at a median follow-up of 28.6 months, 86% of patients with diffuse large B-cell lymphoma who had a response (95% CI, 33 to 98) and 89% of patients with follicular lymphoma who had a response (95% CI, 43 to 98) had maintained the response. Severe cytokine-release syndrome occurred in 5 patients (18%). Serious encephalopathy occurred in 3 patients (11%); 2 cases were self-limiting and 1 case was fatal. All patients in complete remission by 6 months remained in remission at 7.7 to 37.9 months (median, 29.3 months) after induction, with a sustained reappearance of B cells in 8 of 16 patients and with improvement in levels of IgG in 4 of 10 patients and of IgM in 6 of 10 patients at 6 months or later and in levels of IgA in 3 of 10 patients at 18 months or later. CONCLUSIONS: CTL019 cells can be effective in the treatment of relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. High rates of durable remission were observed, with recovery of B cells and immunoglobulins in some patients. Transient encephalopathy developed in approximately one in three patients and severe cytokine-release syndrome developed in one in five patients. (Funded by Novartis and others; ClinicalTrials.gov number, NCT02030834 .).


Assuntos
Imunoterapia Adotiva , Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/terapia , Receptores de Antígenos de Linfócitos T/uso terapêutico , Adulto , Idoso , Antígenos CD19 , Linfócitos B/imunologia , Biomarcadores/análise , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Folicular/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Análise de Sobrevida , Linfócitos T/imunologia
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