Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.182
Filtrar
1.
J Immunother Cancer ; 12(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38955420

RESUMO

BACKGROUND: Fludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepletion despite a lack of clinical safety and efficacy data. To fill this gap in the literature, we evaluated the safety, efficacy, and expansion kinetics of bendamustine as lymphodepletion prior to axicabtagene ciloleucel (axi-cel) therapy. METHODS: 84 consecutive patients with relapsed or refractory large B-cell lymphoma treated with axi-cel and managed with a uniform toxicity management plan at Stanford University were studied. 27 patients received alternative lymphodepletion with bendamustine while 57 received FC. RESULTS: Best complete response rates were similar (73.7% for FC and 74% for bendamustine, p=0.28) and there was no significant difference in 12-month progression-free survival or overall survival estimates (p=0.17 and p=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was similar in both the cohorts. Bendamustine cohort experienced lower proportions of hematological toxicities and antibiotic use for neutropenic fever. Immune reconstitution, as measured by quantitative assessment of cellular immunity, was better in bendamustine cohort as compared with FC cohort. CAR T expansion as measured by peak expansion and area under the curve for expansion was comparable between cohorts. CONCLUSIONS: Bendamustine is a safe and effective alternative lymphodepletion conditioning for axi-cel with lower early hematological toxicity and favorable immune reconstitution.


Assuntos
Cloridrato de Bendamustina , Produtos Biológicos , Linfoma Difuso de Grandes Células B , Humanos , Cloridrato de Bendamustina/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Adulto , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Antígenos CD19/imunologia , Antígenos CD19/uso terapêutico
2.
BMC Nephrol ; 25(1): 225, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009965

RESUMO

BACKGROUND: Membranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20-30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature. CASE PRESENTATION: A 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m2 BSA (body surface area), rituximab 375 mg/m2 BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved. CONCLUSIONS: The mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.


Assuntos
Exantema , Síndrome Nefrótica , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/complicações , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/tratamento farmacológico , Exantema/etiologia , Exantema/tratamento farmacológico , Linfoma de Célula do Manto/complicações , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/diagnóstico , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Rituximab/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Cloridrato de Bendamustina/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem
3.
Acta Med Indones ; 56(2): 249-252, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39010773

RESUMO

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in Western countries after diffuse large B-cell lymphoma. Most patients with FL present with asymptomatic disease. Survival rates have been rising over time mainly due to advancing therapeutic strategiesA-51-year-old male with a history of well-controlled diabetes mellitus treated with insulin presented to the policlinic of hematology-medical oncology with worsening right inguinal lymphadenopathy for >3 months. He had no complaints of prolonged fever, night sweat, or weight loss. Initial physical examination revealed a healthy male with bulky right inguinal lymphadenopathy. The patient was then referred to a surgeon, and excisional biopsy of the enlarged right inguinal lymph nodes was performed. Therefore, stage II bulky symptomatic low-grade FL was established. We administered chemoimmunotherapy with rituximab and bendamustine every 3 weeks for six cycles. The patient tolerated the treatment well and completed six cycles of chemoimmunotherapy, and the follow-up FDG PET/CT showed complete remission of the disease.The patient achieved complete remission after series of chemoimmunotherapy with Bendamustine-Rituximab. Future assessment is still required for this patient to ensure the remission status of the lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Linfoma Folicular , Indução de Remissão , Rituximab , Humanos , Masculino , Linfoma Folicular/tratamento farmacológico , Cloridrato de Bendamustina/administração & dosagem , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
4.
In Vivo ; 38(4): 1740-1749, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38936885

RESUMO

BACKGROUND/AIM: To date, therapeutic options for T-cell acute lymphoblastic leukemia (T-ALL) remain very limited. This study evaluated the efficacy of monotherapies and combination therapies including a selective BCL-2 inhibitor for T-ALL cell lines, namely Jurkat, CCRF-CEM, and Loucy. MATERIALS AND METHODS: Loucy is an early T-precursor ALL (ETP-ALL) cell line characterized by an immature phenotype, whereas Jurkat and CCRF-CEM are late T-cell progenitor ALL (LTP-ALL) cell lines. Monotherapy was conducted with venetoclax, cytarabine, bendamustine, or azacytidine, whereas combination therapy was performed with venetoclax plus cytarabine, venetoclax plus bendamustine, or venetoclax plus azacytidine. Cell viability assay was conducted after 48 h using Trypan blue and the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Statistical analysis for evaluating synergistic interactions between anticancer drugs was performed by using the SynergyFinder Plus and drc R package. RESULTS: Adding venetoclax to cytarabine, bendamustine, or azacitidine achieved an additive effect, with Loewe synergic scores ranging from -10 to 10 in Jurkat and CCRF-CEM. Conversely, the combination of venetoclax and cytarabine displayed an additive effect (Loewe synergic score: 8.45 and 5.82 with MTS and Trypan blue assays, respectively), whereas venetoclax plus bendamustine or azacitidine exhibited a synergistic effect (Loewe synergic score >10 with MTS assay) in Loucy. Remarkably, the Bliss/Loewe score revealed that the combination of venetoclax and bendamustine was the most synergistic, yielding a score of 13.832±0.55. CONCLUSION: The combination of venetoclax and bendamustine demonstrated the greatest synergistic effect in suppressing ETP-ALL cell proliferation. Further studies are warranted to determine the mechanisms for the synergism between venetoclax and bendamustine in high-risk T-ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Compostos Bicíclicos Heterocíclicos com Pontes , Sinergismo Farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Sulfonamidas , Humanos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Jurkat , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 708-717, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38926957

RESUMO

OBJECTIVE: To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine. METHODS: The clinical data of 129 FL patients who were treated with Bendamustine containing regimen were collected from January 1,2020 to October 30,2022 in the Hematology Department of Lianyungang Second People's Hospital and Jiangsu Provincial People's Hospital. The patients were divided into three groups: Bendamustine plus Rituximab (BR), Bendamustine plus Obinutuzumab (GB), Rituximab + Cyclophosphamide + Epirubicin / Doxorubicin + Vindesine + Prednisone (R-CHOP). The efficacy, safety and related prognostic factors of the treatment of FL with a regimen based on Bendamustine were retrospectively analyzed. RESULTS: The ORR was 98% for the BR group, 94% for the GB group, and 72.3% for the R-CHOP group, while the CR rate was 61.2%,70% and 40.4%, respectively. The ORR and CR rates of the R-CHOP group were statistically different from those of the BR group and GB group (P < 0.05). The 3-year PFS rate of the BR group, GB group, and R-CHOP group was 89.6%, 90.9%, 48.9%, respectively. There was a statistically significant difference in 3-year PFS between the R-CHOP group, BR group, and GB group (P < 0.05), while there was no statistically significant difference in 3-year OS(P >0.05). Hematological adverse reactions were mainly bone marrow suppression. Lymphocytes and CD4+T lymphocytes decreased to the lowest level about 6 months after treatment, and the incidence of lymphopenia in BR group and GB group was higher than that in R-CHOP group, with a statistical difference (P < 0.05). The higher incidence of non-Hematological adverse reactions were pulmonary infection, EB virus infection, hepatitis B virus reactivation, and gastrointestinal reactions without statistical difference in 3 groups (P >0.05), and were all controllable. The Receiver operating characteristic of CD4+T lymphocyte count showed that AUC of BR group was 0.802, and the critical value was 258/uL; AUC of GB group was 0.754 with a critical value of 322/uL. CONCLUSION: The treatment of FL with the Bendamustine containing regimen has good efficacy and controllable adverse reactions, but lymphocytopenia was significant after treatment, and the curative efficacy in combination with various CD20 monoclonal antibodies was different. The lowest CD4+T lymphocyte count can be used as a predictive factor for the occurrence of infection and efficacy of the Bendamustine containing regimen for FL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Linfócitos T CD4-Positivos , Linfoma Folicular , Rituximab , Humanos , Cloridrato de Bendamustina/administração & dosagem , Linfoma Folicular/tratamento farmacológico , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Doxorrubicina/administração & dosagem , Ciclofosfamida , Prednisona/administração & dosagem , Adulto , Prognóstico , Infecções , Resultado do Tratamento , Vincristina
6.
Oncol Res ; 32(6): 1031-1036, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827319

RESUMO

Extranodal marginal zone lymphoma (EMZL) encompasses 70% of cases of marginal zone lymphoma. Frontline bendamustine and rituximab (BR) were derived from trials involving other indolent non-Hodgkin's lymphomas. Only one trial has evaluated frontline BR prospectively in EMZL. This retrospective study reports outcomes among EMZL patients receiving frontline BR. Twenty-five patients were included with a median age of 69 years (40-81). Five (20.0%) patients had stage I/II disease, and 20 (80.0%) had stage III/IV disease. The median number of cycles was 6.0 (3.0-6.0). Maintenance rituximab was administered to 10 (41.7%) individuals. Overall response rate (ORR) was 100.0% (60.0% complete response, 40.0% partial response). Medians of overall survival and progression-free survival were not reached. The estimated 2-year progression-free survival was 85.2% and overall survival was 100.0%. Four (16.6%) patients had infections related to treatment; 3 (12.0%) transformed to diffuse large B-cell lymphoma; 5 (20.8%) had a relapse or progression of EMZL; and 3 (12.0%) died unrelated to BR. BR is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Linfoma de Zona Marginal Tipo Células B , Rituximab , Humanos , Cloridrato de Bendamustina/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Idoso , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/patologia , Pessoa de Meia-Idade , Feminino , Masculino , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Estadiamento de Neoplasias , Intervalo Livre de Progressão
7.
Lancet Haematol ; 11(6): e406-e414, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38796193

RESUMO

BACKGROUND: Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL. METHODS: Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375). FINDINGS: 86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown). INTERPRETATION: Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial. FUNDING: Bristol-Myers Squibb. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.


Assuntos
Azacitidina , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Azacitidina/uso terapêutico , Azacitidina/efeitos adversos , Azacitidina/administração & dosagem , Administração Oral , Cloridrato de Bendamustina/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Gencitabina , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/mortalidade , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Depsipeptídeos/uso terapêutico , Depsipeptídeos/efeitos adversos , Depsipeptídeos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Idoso de 80 Anos ou mais
8.
Am J Hematol ; 99(6): 1192-1195, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38578022
9.
Leuk Lymphoma ; 65(7): 911-921, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38598516

RESUMO

Parsaclisib, a potent and highly selective phosphoinositide 3-kinase δ inhibitor, has shown clinical activity in relapsed/refractory (R/R) B-cell lymphoma. The phase 1 CITADEL-112 (NCT03424122) study assessed safety and efficacy of parsaclisib in combination with investigator choice standard of care (SOC; rituximab [Treatment A], rituximab plus bendamustine [Treatment B], or ibrutinib [Treatment C]) in 50 patients with R/R B-cell lymphoma. The most common treatment-emergent adverse events included neutropenia (62.5%, 50.0%, and 50.0% of patients in Treatments A, B, and C, respectively); diarrhea (37.5%) and anemia (31.3%) in Treatment A; abdominal pain, asthenia, diarrhea, and nausea (each 33.3%) in Treatment B; and increased alanine and aspartate aminotransferase (each 37.5%) in Treatment C. Objective responses were observed in 13 patients (81.3%) in Treatment A, 10 (55.6%) in Treatment B, and 8 (50.0%) in Treatment C. Parsaclisib combined with SOC therapies had an expected safety profile and promising efficacy in patients with R/R B-cell lymphomas.


Assuntos
Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Linfoma de Células B , Piperidinas , Rituximab , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Masculino , Feminino , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Pessoa de Meia-Idade , Idoso , Adenina/análogos & derivados , Adenina/administração & dosagem , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico
10.
Eur J Haematol ; 113(2): 218-226, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38661269

RESUMO

BACKGROUND: There are few reports of clinical practice treatment patterns and efficacy in mantle cell lymphoma (MCL). MATERIALS AND METHODS: We retrospectively studied a large, multicenter, cohort of patients with MCL diagnosed between 2000 and 2020 in eight institutions. RESULTS: 536 patients were registered (73% male, median of 70 years). Front-line treatment was based on high-dose cytarabine, bendamustine, and anthracyclines in 42%, 12%, and 15%, respectively. The median PFS for all patients was 45 months; 68, 34, and 30 months for those who received high-dose cytarabine-based, bendamustine-based and anthracycline-based therapy. 204 patients received second-line. Bendamustine-based treatment was the most common second-line regimen (36% of patients). The median second-line PFS (sPFS) for the entire cohort was 14 months; 19, 24, and 31 for bendamustine-, platinum-, and high-dose cytarabine-based regimens, with broad confidence intervals for these latter estimates. Patients treated with cytarabine-based therapies in the front-line and those with front-line PFS longer than 24 months had a substantially superior sPFS. CONCLUSION: Front-line treatment in this cohort of MCL was as expected and with a median PFS of over 3.5 years. Second-line treatment strategies were heterogeneous and the median second-line PFS was little over 1 year.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Célula do Manto , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/diagnóstico , Masculino , Idoso , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso de 80 Anos ou mais , Adulto , Resultado do Tratamento , Citarabina/uso terapêutico , Citarabina/administração & dosagem , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/uso terapêutico , Gerenciamento Clínico , Estadiamento de Neoplasias , Retratamento
11.
Clin J Gastroenterol ; 17(3): 461-465, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38607542

RESUMO

A 61-year-old man present to us with continued abdominal pain without abdominal tenderness for 1 month. Blood testing showed elevated biliary enzymes and inflammation. Contrast-enhanced computed tomography (CT) revealed thickening of the transverse colon with relatively strong enhancement but no bile duct dilatation. Colonoscopy revealed localized edema and granular mucosa in the transverse colon. Fluoroscopic endoscopy exhibited the absence of haustra. Multiple biopsies were performed, but differentiation between mild inflammation and mucosa-associated lymphoid tissue (MALT) lymphoma was inconclusive. To establish a definitive diagnosis, transgastric endoscopic ultrasound-guided fine needle biopsy of the hypoechoic mass was performed. Histopathological analysis exhibited the proliferation of small-sized lymphocytes. Fluorescence in situ hybridization revealed the characteristic API2-MALT1 translocation of MALT lymphoma. We performed liver biopsy to investigate biliary enzyme elevation. Histopathology confirmed lymphocytic infiltration within Glisson's capsule. Immunohistochemistry showed positive for CD20 and negative for CD3 and CD5, signifying the infiltration of MALT lymphoma in the liver. Based on these findings, we diagnosed MALT lymphoma, Lugano classification Stage IV. We performed bendamustine-rituximab (BR)-combined therapy. After six courses of BR-combined therapy, colonoscopy revealed improvement in the lead pipe sign and CT revealed disappearance of the mass.


Assuntos
Colo Transverso , Neoplasias do Colo , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Linfoma de Zona Marginal Tipo Células B , Humanos , Masculino , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Pessoa de Meia-Idade , Colo Transverso/patologia , Colo Transverso/diagnóstico por imagem , Neoplasias do Colo/patologia , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/diagnóstico , Rituximab/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colonoscopia , Cloridrato de Bendamustina/administração & dosagem , Tomografia Computadorizada por Raios X
12.
J Hematol Oncol ; 17(1): 19, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644469

RESUMO

Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31). Patients were evaluated for toxicities and responses. Of note, 7 patients (22.6%) would have dnot met the inclusion criteria for the registrational liso-cel clinical trials, mostly due to older age. Overall and complete response rates were 76.9% and 73.1%, respectively. At a median follow-up of 6.3 months, the 6-month progression-free and overall survival were 59.9% and 91.1%, respectively. Rates of cytokine-release syndrome (CRS) and neurotoxicity (ICANS) of any grade were 9.7% and 9.7%, respectively, with no grade ≥ 3 events. No infections were reported during the first 30 days following liso-cel infusion. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.


Assuntos
Cloridrato de Bendamustina , Imunoterapia Adotiva , Humanos , Cloridrato de Bendamustina/uso terapêutico , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Estudos Retrospectivos , Adulto , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Alquilantes/efeitos adversos , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Idoso de 80 Anos ou mais , Resultado do Tratamento
13.
BMJ Case Rep ; 17(4)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627054

RESUMO

Extramedullary relapse in patients with multiple myeloma (MM) is often associated with loss of biochemical response and the appearance of measurable residual disease in the bone marrow. Fever is an unusual presenting manifestation of MM. Treatment of extramedullary relapse in patients progressing on proteasome inhibitors, anti-CD38 monoclonal antibodies and immunomodulatory drugs is challenging, as access to chimeric antigen receptor T-cells and bispecific antibodies is limited. We report a case of relapsed MM who presented with fever and hepatic space-occupying lesion mimicking hepatocellular carcinoma. In this case report, we also present our experience of using a novel combination regimen comprising Dara-Pom-Benda-Dexa (daratumumab, pomalidomide, dexamethasone and bendamustine) for relapsed MM.


Assuntos
Mieloma Múltiplo , Talidomida/análogos & derivados , Humanos , Mieloma Múltiplo/patologia , Cloridrato de Bendamustina/uso terapêutico , Dexametasona/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Fígado/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
14.
Br J Haematol ; 204(6): 2233-2236, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38504454

RESUMO

The bendamustine-rituximab (BR) schedule is an efficient first-line therapy in Waldenström macroglobulinaemia (WM). A previous analysis of 69 patients who received this treatment confirmed a high response rate and good progression-free (PFS) and overall survival (OS). With a median follow-up of 76.1 months (95% confidence interval [CI] 69.9-80.6), 5-year outcome is still excellent at 66.63% (95% CI 56.09-79.17) for PFS and 80.01% (95% CI 70.82-90.41) for OS. The rate of secondary cancers is 17.66% (IQR 7.99-27.64) at 66 months. Relapsed patients who received ibrutinib as second-line clearly benefited from this schedule. This confirms current recommendations suggesting BR long-term efficacy as first-line option in WM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Rituximab , Macroglobulinemia de Waldenstrom , Humanos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/mortalidade , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , França , Seguimentos , Resultado do Tratamento
15.
Int J Hematol ; 119(6): 677-685, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38519820

RESUMO

Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8 weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Progressão da Doença , Fluordesoxiglucose F18 , Linfoma Folicular , Tomografia por Emissão de Pósitrons , Rituximab , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/mortalidade , Cloridrato de Bendamustina/administração & dosagem , Rituximab/administração & dosagem , Fluordesoxiglucose F18/administração & dosagem , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Japão , Tomografia por Emissão de Pósitrons/métodos , Recidiva , Idoso de 80 Anos ou mais , Compostos Radiofarmacêuticos/administração & dosagem
16.
Transplant Cell Ther ; 30(7): 726.e1-726.e8, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38494076

RESUMO

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory mantle cell lymphoma (MCL). During a fludarabine shortage, we used bendamustine as an alternative to standard cyclophosphamide/fludarabine (cy/flu) lymphodepletion (LD) prior to brexu-cel. We assessed MCL patient outcomes as well as CAR T-cell expansion and persistence after brexu-cel following bendamustine or cy/flu LD at our center. This was a retrospective single institution study that utilized prospectively banked blood and tissue samples. Clinical efficacy was assessed by 2014 Lugano guidelines. CAR T-cell expansion and persistence in peripheral blood were assessed on day 7 and at ≥month 6 for patients with available samples. Seventeen patients received bendamustine and 5 received cy/flu. For the bendamustine cohort, 14 (82%) received bridging therapy and 4 (24%) had CNS involvement. Fifteen patients (88%) developed CRS with 4 (24%) ≥grade 3 events. Six (35%) patients developed ICANS with 4 (24%) events ≥grade 3. No patient had ≥grade 3 cytopenias at day 90. Best objective (BOR) and complete response (CRR) rates were 82% and 65%, respectively. At 24.5 months median follow-up, 12-month progression-free survival (PFS) was 45%, 24-month PFS was 25%, and median duration of response was 19 months. Median OS was not reached. BOR was 25% (1/4) for patients with CNS involvement. CAR transgene expansion after bendamustine LD was observed on day 7 in all (4/4) patients tested and persisted at ≥6 months (2/2), regardless of response. Bendamustine LD before brexu-cel for MCL is feasible and safe with a lower frequency and shorter duration of cytopenias than reported for cy/flu. Both CAR T-cell expansion and persistence were observed after bendamustine LD. Outcomes appear comparable to the real world outcomes reported with cy/flu LD.


Assuntos
Cloridrato de Bendamustina , Imunoterapia Adotiva , Linfoma de Célula do Manto , Humanos , Cloridrato de Bendamustina/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Linfoma de Célula do Manto/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Imunoterapia Adotiva/métodos , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/administração & dosagem , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Alquilantes/administração & dosagem , Antígenos CD19/imunologia , Resultado do Tratamento
17.
Br J Haematol ; 205(1): 146-157, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38485116

RESUMO

Infection and lymphopenia are established bendamustine-related complications. The relationship between lymphopenia severity and infection risk, and the role of antimicrobial prophylaxis, is not well described. This multicentre retrospective study analysed infection characteristics and antimicrobial prophylaxis in 302 bendamustine-treated indolent non-Hodgkin lymphoma patients. Lymphopenia (<1 × 109/L) was near universal and time to lymphocyte recovery correlated with cumulative bendamustine dose. No association between lymphopenia severity and duration with infection was observed. Infections occurred in 44% of patients (50% bacterial) with 27% hospitalised; 32% of infections occurred ≥3 months post bendamustine completion. Infection was associated with obinutuzumab and/or maintenance anti-CD20 therapy, prior therapy and advanced stage. Twenty-four opportunistic infections occurred in 21 patients: ten varicella zoster virus (VZV), seven herpes simplex virus (HSV), one cytomegalovirus, one progressive multifocal leucoencephalopathy, one nocardiosis, one Pneumocystis jiroveci pneumonia (PJP) and three other fungal infections. VZV/HSV and PJP prophylaxis were prescribed to 42% and 54% respectively. Fewer VZV/HSV infections occurred in patients receiving prophylaxis (HR 0.14, p = 0.061) while PJP prophylaxis was associated with reduced risk of bacterial infection (HR 0.48, p = 0.004). Our study demonstrates a significant infection risk regardless of lymphopenia severity and supports prophylaxis to mitigate the risk of early and delayed infections.


Assuntos
Cloridrato de Bendamustina , Linfoma não Hodgkin , Linfopenia , Infecções Oportunistas , Humanos , Cloridrato de Bendamustina/uso terapêutico , Cloridrato de Bendamustina/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Masculino , Linfoma não Hodgkin/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Linfopenia/induzido quimicamente , Adulto , Infecções Oportunistas/prevenção & controle , Idoso de 80 Anos ou mais , Antibioticoprofilaxia/métodos , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/uso terapêutico
18.
Haematologica ; 109(7): 2297-2302, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38497158
20.
In Vivo ; 38(2): 923-927, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38418128

RESUMO

BACKGROUND/AIM: Patients with malignant lymphoma, in a latent state of weakened immune function, are at risk of chemotherapy-induced immunosuppression and cytomegalovirus (CMV) infection. Concomitant therapy with bendamustine and rituximab or obinutuzumab intensifies immunosuppression, potentially affecting CMV onset. This study aimed to assess CMV onset differences between bendamustine monotherapy and combination therapy with rituximab or obinutuzumab using the Japanese Adverse Drug Event Report database (JADER). PATIENTS AND METHODS: A JADER analysis dataset (April 2004 to September 2022) defined CMV infection using 31 preferred term (PT) words from MedDRA 25.1J HLT "Cytomegalovirus infection (10011827)". Reporting odds ratios (ROR) calculated CMV infection signals for bendamustine monotherapy, rituximab, obinutuzumab, bendamustine+rituximab (BR), and bendamustine+obinutuzumab (GB). ROR confidence intervals exceeding 1 indicated a CMV signal. Days of CMV infection were calculated based on adverse event onset and administration start. RESULTS: CMV signals were confirmed for monotherapy and combination therapies. CMV infection durations (median, interquartile range) were 41.0 days (23.5-69.5) for bendamustine monotherapy, 63.5 days (35.2-95.0) for BR, and 61.0 days (33.0-102.5) for GB, with cases exceeding 200 days. CONCLUSION: JADER analysis detected significant CMV signals for rituximab, obinutuzumab, and bendamustine. Caution may be warranted 7-9 months post-bendamustine administration, necessitating further investigation, including cell-mediated immunity suppression assessment.


Assuntos
Infecções por Citomegalovirus , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Cloridrato de Bendamustina/efeitos adversos , Rituximab/efeitos adversos , Citomegalovirus , Preparações Farmacêuticas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Infecções por Citomegalovirus/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA