Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 246
Filtrar
2.
4.
JCO Oncol Pract ; : OP2000020, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32997608

RESUMO

The role of clinical researchers is vital to cancer progress. The teaching, research, and leadership roles that academic oncologists hold need to be accounted for and appropriately compensated. National metrics are currently inexistent, but are necessary to move the oncology research field forward. Clinical research and routine clinical care must be harmoniously integrated without competing. This article reviews the national landscape of clinical cancer research and proposes a call for action.

5.
Oncology (Williston Park) ; 34(9): 343, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32965661

RESUMO

During the height of the coronavirus disease 2019(COVID-19) pandemic, many health care facilities needed to focus on screening for and treating patients with known or suspected COVID-19. This resulted in the diversion of health care workers and resources.


Assuntos
Infecções por Coronavirus , Diagnóstico Tardio , Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias/diagnóstico , Neoplasias/mortalidade , Pandemias , Pneumonia Viral , Betacoronavirus , Simulação por Computador , Humanos
6.
Oncology (Williston Park) ; 34(7): 244, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32674205

RESUMO

Now that the world has been dealing with the coronavirus disease 2019 (COVID-19) pandemic for several months, we have learned so much. Some of the modifications we have made have been "good" and will hopefully help oncology care, education, and research going forward. Here are some of the issues and changes that the pandemic engendered.


Assuntos
Inovação Organizacional , Telemedicina/métodos , Betacoronavirus , Pesquisa Biomédica , Ensaios Clínicos como Assunto/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/tendências , Humanos , Oncologia/métodos , Oncologia/organização & administração , Oncologia/tendências , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Telecomunicações/tendências
9.
J Clin Oncol ; 38(27): 3119-3128, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32401634

RESUMO

PURPOSE: Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication. PATIENTS AND METHODS: Data were collected retrospectively from all patients with relapsed/refractory LBCL who underwent leukapheresis as of September 30, 2018, at 17 US institutions with the intent to receive SOC axi-cel. Toxicities were graded and managed according to each institution's guidelines. Responses were assessed as per Lugano 2014 classification. RESULTS: Of 298 patients who underwent leukapheresis, 275 (92%) received axi-cel therapy. Compared with the registrational ZUMA-1 trial, 129 patients (43%) in this SOC study would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis. Among the axi-cel-treated patients, grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 7% and 31%, respectively. Nonrelapse mortality was 4.4%. Best overall and complete response rates in infused patients were 82% (95% CI, 77% to 86%) and 64% (95% CI, 58% to 69%), respectively. At a median follow-up of 12.9 months from the time of CAR T-cell infusion, median progression-free survival was 8.3 months (95% CI, 6.0 to15.1 months), and median overall survival was not reached. Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 and elevated lactate dehydrogenase had shorter progression-free and overall survival on univariable and multivariable analysis. CONCLUSION: The safety and efficacy of axi-cel in the SOC setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.

10.
Blood Adv ; 4(2): 253-262, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31945157

RESUMO

There is a paucity of data regarding outcomes and response to standard therapy in patients with limited-stage (LS) agressive B-cell lymphoma (LS-ABCL) who harbor MYC rearrangement (MYC-R) with or without BCL2 and/or BCL6 rearrangements. We conducted a multicenter retrospective study of MYC-R LS-ABCL patients who received either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or more intensive immunochemotherapy (IIC) plus or minus consolidative involved-field radiation therapy (IFRT). One hundred four patients from 15 academic centers were included. Forty four patients (42%) received R-CHOP, of whom 52% had IFRT. Sixty patients (58%) received IIC, of whom 40% had IFRT. Overall response rate was 91% (84% complete response [CR]; 7% partial response). Patients with double-hit lymphoma (DHL; n = 40) had a lower CR rate compared with patients with MYC-R only (75% vs 98%; P = .003). CR rate was higher in the IFRT vs no-IFRT group (98% vs 72%; P < .001). Median follow-up was 3.2 years; 2-year progression-free survival (PFS) and overal survival (OS) were 78% and 86% for the entire cohort, and 74% and 81% for the DHL patients, respectively. PFS and OS were similar across treatment groups (IFRT vs no IFRT, R-CHOP vs IIC) in the entire cohort and in DHL patients. Our data provide a historical benchmark for MYC-R LS-ABCL and LS-DHL patients and show that outcomes for this population may be better than previously recognized. There was no benefit of using IIC over R-CHOP in patients with MYC-R LS-ABCL and LS-DHL.

12.
Clin Lymphoma Myeloma Leuk ; 19(12): 751-757, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31648957

RESUMO

Adoptive cellular immunotherapy with anti CD19 chimeric antigen receptor (CAR)-T cell has changed the treatment landscape in relapsed/refractory B cell lymphomas. They have emerged as effective therapy in patients with multiple relapsed/refractory disease, capable of sustaining durable remissions. Two CAR-T cell products (axicabtagene ciloleucel and tisagenlecleucel) are currently approved by the United States Food and Drug Administration. A third anti CD19 CAR-T cell, lisocabtagene ciloleucel is currently being evaluated in large clinical trials and may also be United States Food and Drug Administration-approved soon. CAR-T cell-related toxicities, including infections, cytokine release syndrome, and neurotoxicity are potential complications of therapy. With increasing use of CAR-T cells, the mechanism of toxicities and mitigation strategies needs to be developed. Additionally, reasons for CAR-T cell failure and progression following this therapy needs to be further studied. We describe the recent developments in this field, with emphasis on the complications of therapy and factors contributing to toxicities, efficacy, and resistance. We also describe the ongoing research in this field and the newer CAR-T cell constructs that are being developed to counter the challenges that have been identified in this field.


Assuntos
Imunoterapia Adotiva , Linfoma não Hodgkin/terapia , Animais , Estudos Clínicos como Assunto , Engenharia Genética , Custos de Cuidados de Saúde , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/economia , Imunoterapia Adotiva/métodos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/mortalidade , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo , Resultado do Tratamento
13.
Sci Transl Med ; 11(497)2019 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217338

RESUMO

The activated B cell (ABC-like) subtype of diffuse large B cell lymphoma (DLBCL) is characterized by chronic activation of signaling initiated by immunoglobulin µ (IgM). By analyzing the DNA copy number profiles of 1000 DLBCL tumors, we identified gains of 18q21.2 as the most frequent genetic alteration in ABC-like DLBCL. Using integrative analysis of matched gene expression profiling data, we found that the TCF4 (E2-2) transcription factor gene was the target of these alterations. Overexpression of TCF4 in ABC-like DLBCL cell lines led to its occupancy on immunoglobulin (IGHM) and MYC gene enhancers and increased expression of these genes at the transcript and protein levels. Inhibition of TCF4 activity with dominant-negative constructs was synthetically lethal to ABC-like DLBCL cell lines harboring TCF4 DNA copy gains, highlighting these gains as an attractive potential therapeutic target. Furthermore, the TCF4 gene was one of the top BRD4-regulated genes in DLBCL cell lines. BET proteolysis-targeting chimera (PROTAC) ARV771 extinguished TCF4, MYC, and IgM expression and killed ABC-like DLBCL cells in vitro. In DLBCL xenograft models, ARV771 treatment reduced tumor growth and prolonged survival. This work highlights a genetic mechanism for promoting immunoglobulin signaling in ABC-like DLBCL and provides a functional rationale for the use of BET inhibitors in this disease.


Assuntos
Imunoglobulinas/metabolismo , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Fator de Transcrição 4/genética , Animais , Western Blotting , Linhagem Celular , Sobrevivência Celular , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Camundongos , Camundongos Nus , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Natl Compr Canc Netw ; 17(6): 650-661, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31200358

RESUMO

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin's lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.


Assuntos
Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/terapia , Oncologia/normas , Recidiva Local de Neoplasia/terapia , Adulto , Assistência ao Convalescente/normas , Antineoplásicos Imunológicos/normas , Antineoplásicos Imunológicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/normas , Linfoma Folicular/imunologia , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Oncologia/métodos , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Inibidores de Fosfoinositídeo-3 Quinase/normas , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Estados Unidos
15.
Future Oncol ; 15(18): 2113-2124, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31144521

RESUMO

Aim: To examine whether the center type and socioeconomic factors significantly impact 1-month mortality and overall survival (OS) of patients with diffuse large B-cell lymphoma (DLBCL). Methods: National Cancer Database (NCDB) was used to identify patients diagnosed with diffuse large B-cell lymphoma from 2006 to 2012 (postrituximab era). Results: Among 185,183 patients, 33% were treated at academic centers. The receipt of therapy at larger volume centers was associated with improved 1-month mortality. Academic centers had better OS than nonacademic centers in univariable analysis. Younger age, private insurance, lower Charlson comorbidity score and lower lymphoma stage were associated with improved 1-month mortality and OS. Conclusion: The receipt of therapy at larger volume centers and socioeconomic factors were associated with improved survival.


Assuntos
Instalações de Saúde , Linfoma Difuso de Grandes Células B/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Bases de Dados Factuais , Feminino , Instalações de Saúde/classificação , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Mortalidade , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Estudos Retrospectivos , Fatores Socioeconômicos , Estados Unidos/epidemiologia
16.
Oncology (Williston Park) ; 33(5): 192-8, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31095720

RESUMO

Hodgkin lymphoma is a highly curable malignancy, with an excellent prognosis. However, around 10% to 25% of patients will have primary refractory or relapsed disease, despite using risk-adapted strategies. The standard of care for patients with relapsed/refractory Hodgkin lymphoma has been cytoreduction using salvage chemotherapy, followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT). Studies have shown that AHSCT produces a durable response rate of 50%, and that patients achieve a complete response with salvage chemotherapy. The outcomes for patients who do not respond to salvage chemotherapy or relapse after an AHSCT have been poor, with a median survival of 25 months. However, with the approval of novel agents over the last decade, the outcomes for patients with relapsed/refractory Hodgkin lymphoma have improved significantly. In this article, we present a case of a patient with relapsed Hodgkin lymphoma who responded to salvage chemotherapy incorporating brentuximab vedotin, a novel agent.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Terapia de Salvação , Resultado do Tratamento , Adulto Jovem
18.
Leuk Lymphoma ; 60(9): 2255-2263, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30848966

RESUMO

Mantle cell lymphoma (MCL) is a rare cancer with diverse management options. Although clinical practice guidelines have become ubiquitous across medicine, the utility of guidelines for MCL management is limited by provider awareness and the lack of a definitive standard of care. We sought to determine whether expert recommendations, delivered as an online decision support tool, impacted practitioners' therapeutic decisions with MCL. Participants were more likely than the experts to select aggressive regimens for both newly diagnosed and relapsed/refractory MCL. After seeing the expert recommendations, participants revealed that the expert opinion impacted their treatment choices in 103 of 365 clinical scenarios, suggesting that online decision support tools may increase the number of clinicians making treatment decisions for patients with MCL that are concordant with expert consensus recommendations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tomada de Decisão Clínica/métodos , Sistemas de Apoio a Decisões Clínicas , Linfoma de Célula do Manto/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Consenso , Resistencia a Medicamentos Antineoplásicos , Humanos , Internet , Linfoma de Célula do Manto/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Guias de Prática Clínica como Assunto
19.
Lancet Haematol ; 6(2): e100-e109, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30709431

RESUMO

BACKGROUND: Therapeutic approaches for B-cell malignancies continue to evolve, especially with regard to combination approaches. We assessed the safety and efficacy of the triplet ublituximab, umbralisib, and ibrutinib in patients with advanced B-cell malignancies. METHODS: We did an open-label, phase 1 study with dose-escalation and dose-expansion phases, at five centres in the USA. Eligible patients were aged 18 years or older with histologically confirmed lymphocytic leukaemia or relapsed or refractory B-cell non-Hodgkin lymphoma, had measurable disease, adequate organ function, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Patients with known CNS lymphoma, active hepatitis B or C infection, or HIV were excluded. In the dose-escalation cohort, patients were treated in cycles of 28 days with escalating doses of oral umbralisib (400, 600, or 800 mg) and fixed doses of intravenous ublituximab (900 mg) and oral ibrutinib (420 mg for patients with chronic lymphocytic leukaemia; 560 mg for patients with B-cell non-Hodgkin lymphoma) in a standard 3 × 3 design until disease progression or intolerance. In the dose-expansion phase, patients were given the recommended dose of the drug combination as determined from the dose-escalation phase. The primary endpoints were safety, dose-limiting toxicities, and the maximum tolerated dose of umbralisib, when given in combination with ublituximab and ibrutinib. Safety was assessed in patients who received at least one dose of study drug; activity was assessed in all patients who had at least one post-treatment efficacy measurement. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT02006485. FINDINGS: Between Sept 2, 2014, and Nov 6, 2017, we enrolled 46 patients: 24 in the dose-escalation cohort (n=14 chronic lymphocytic leukaemia or small lymphocytic lymphoma; n=10 B-cell non-Hodgkin lymphoma) and 22 in the dose-expansion cohort (n=9 chronic lymphocytic leukaemia or small lymphocytic lymphoma; n=13 B-cell non-Hodgkin lymphoma). 46 patients received at least one dose of study drug. The maximum tolerated dose of umbralisib was not reached. The recommended dose for the dose-expansion phase was umbralisib 800 mg orally once daily plus ibrutinib orally once daily and intravenous ublituximab 900 mg administered on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6, and on day 1 of cycles 9 and 12. 37 (84%) of 44 patients achieved an overall response (complete or partial response). The most common any-grade adverse events were diarrhoea (n=27 [59%]), fatigue (n=23 [50%]), infusion-related reaction (n=20 [43%]), dizziness (n=17 [37%]), nausea (n=17 [37%]), and cough (n=16 [35%]). Grade 3-4 adverse events were manageable with the most common being neutropenia (n=10 [22%]) and cellulitis (n=6 [13%]). Serious adverse events occurred in 11 (24%) of 46 patients and included rash (n=2 [4%]), pneumonia (n=2 [4%]), atrial fibrillation (n=2 [4%]), sepsis (n=2 [4%]), abdominal pain (n=1 [2%]), syncope (n=1 [2%]), cellulitis (n=1 [2%]), pneumonitis (n=1 [2%]), headache (n=1 [2%]), lung infection (n=1 [2%]), skin infection (n=1 [2%]), pleural effusion (n=1 [2%]), pericardial infusion (n=1 [2%]), upper gastrointestinal bleeding (n=1 [2%]), diarrhoea (n=1 [2%]), and weakness (n=1 [2%]). No deaths related to adverse events occurred. INTERPRETATION: The combination of ublituximab, umbralisib, and ibrutinib seems to be tolerable and is associated with encouraging activity in advanced chronic lymphocytic leukaemia and B-cell non-Hodgkin lymphoma. This triplet combination will require further investigation in future studies to improve understanding of this novel, chemotherapy-free triplet combination in the management of these cancers. FUNDING: TG Therapeutics.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Segurança , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico
20.
J Clin Oncol ; 37(6): 471-480, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30615550

RESUMO

PURPOSE: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS: We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed. RESULTS: Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION: In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto/terapia , Rituximab/uso terapêutico , Adulto , Fatores Etários , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , América do Norte , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Rituximab/efeitos adversos , Fatores de Tempo , Transplante Autólogo , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA