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1.
Biochem Med (Zagreb) ; 30(1): 010801, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31839726

RESUMO

This is a case report of a challenging diagnosis of IgE monoclonal gammopathy of undetermined significance, which transformed into myeloma, then transformed into IgE-producing plasma cell leukaemia in a 71-year-old male who was followed in Brest, France, from 2015 to 2019. The IgE-producing variant is the rarest sub-type of multiple myeloma, and plasma cell leukaemia is considered to be the rarest and the most aggressive of human monoclonal gammopathies. In November 2015, hypogammaglobulinemia was detected during a systematic check-up. A kappa light chain monoclonal gammopathy was first diagnosed due to an increase of the free kappa/lambda light chains ratio. No monoclonal immunoglobulin was detected by either serum protein electrophoresis (Capillarys 2, Sebia, Issy-les-Moulineaux, France) or immunofixation (Hydrasys 2, Sebia, Issy-les-Moulineaux, France). In June 2018, a blood smear led to the diagnosis of plasma cell leukaemia. A monoclonal peak was detected and identified as IgE-kappa. Analysis of an archival sample taken three years earlier, revealed the presence of a monoclonal IgE, which had been missed at diagnosis. Chemotherapy with bortezomib and dexamethasone was introduced. The patient survived 10 months after the diagnosis of leukaemia. This case shows that an abnormal free light chain ratio should be considered as a possible marker of IgE monoclonal gammopathy even in the absence of a solitary light chain revealed by immunofixation. In addition, the use of an undiluted serum may increase the sensitivity of the immunofixation for the detection of IgE monoclonal gammopathies compared to the 1:3 dilution recommended by the manufacturer.


Assuntos
Imunoglobulina E/metabolismo , Leucemia Plasmocitária/diagnóstico , Idoso , Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Leucemia Plasmocitária/tratamento farmacológico , Masculino , Paraproteinemias/diagnóstico , Plasmócitos/patologia
2.
Anticancer Res ; 39(9): 5003-5007, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519607

RESUMO

Incorporating bortezomib and/or lenalidomide in the management of plasmablastic lymphoma is an attractive option due to the reported high response rates. However, concerns about overlapping toxicities can deter clinicians from incorporating these novel agents into chemotherapy. In this case report we describe a patient with plasmablastic lymphoma, who received both lenalidomide and bortezomib as part of upfront treatment for a high-risk plasmablastic lymphoma. After completing intensive chemotherapy, the patient was transitioned to a regimen of daily lenalidomide and biweekly bortezomib to decrease the chance of relapse. This maintenance phase was given for 6 months and was well tolerated. Despite having multiple adverse risk factors, the patient remains in remission, 18 months following diagnosis.


Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Linfoma Plasmablástico/tratamento farmacológico , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Bortezomib/administração & dosagem , Gerenciamento Clínico , Feminino , Humanos , Quimioterapia de Indução , Imagem por Ressonância Magnética , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Linfoma Plasmablástico/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
3.
J Assoc Physicians India ; 67(7): 54-57, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559769

RESUMO

Introduction: Multiple myeloma (MM) is a neoplastic clonal plasma cell disorder. Approximately 30% of newly diagnosed MM present with baseline renal dysfunction adversely affecting prognosis and survival. But its outcome has improved with the advent of novel agents. Methods: We undertook this clinicopathological study to assess the profile of renal involvement, evaluate hematological response, renal reversibility and renal response of 34 newly diagnosed cases of MM with renal impairment receiving 4-6 cycles of Bortezomib, Thalidomide and Dexamethasone (BTD). Results: Bone pain (67.64%) and pallor (88.23%) were the most common clinical symptom and sign respectively. Mean serum creatinine before and after treatment was 3.5 mg/dl and 1.59 mg/dl respectively. After treatment 15 cases achieved renal reversibility, 8 patients had improved renal function and 3 patients became dialysis independent. The median time to renal reversal was 22weeks (2-28 weeks) and overall myeloma response rate was 78.78%. All patients showed renal response. The median time to renal response was 2.4weeks. We found 38.23% pure cast nephropathy, 14.7% myeloma immunoglobulin deposition disease (MIDD), 5.88% amylodosis apart from other lesions. Conclusion: BTD is safe, effective in reversing renal impairment and improves survival in newly diagnosed cases of MM with renal impairment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/uso terapêutico , Humanos , Resultado do Tratamento
5.
G Ital Nefrol ; 36(4)2019 Jul 24.
Artigo em Italiano | MEDLINE | ID: mdl-31373468

RESUMO

In the last few years, the increasing awareness of the complex interaction between monoclonal component and renal damage has determined not only a new classification of the associated disorders, called Monoclonal Gammopathy of Renal Significance (MGRS), but has also contributed to emphasize the importance of an early diagnosis of the renal involvement, which is often hard to detect but can evolve towards terminal uraemia; it has also pointed at the need to treat these disorders with aggressive regimens, even if they are not strictly neoplastic. The case described here presented urinary abnormalities and renal failure secondary to a membranoproliferative glomerulonephritis (MPGN), with intensively positive immunofluorescence (IF) for monoclonal k light chain and C3, and in the absence of a neoplastic lympho-proliferative disorder documented on bone marrow biopsy. After the final diagnosis of MGRS, the patient was treated with several cycles of a therapy including dexamethasone, cyclophosphamide and bortezomib, showing a good functional and clinical response.


Assuntos
Glomerulonefrite Membranoproliferativa/complicações , Paraproteinemias/complicações , Insuficiência Renal/etiologia , Biópsia , Bortezomib/uso terapêutico , Complemento C3c , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Diagnóstico Precoce , Feminino , Glomerulonefrite Membranoproliferativa/diagnóstico , Glomerulonefrite Membranoproliferativa/patologia , Glucocorticoides/uso terapêutico , Humanos , Cadeias kappa de Imunoglobulina , Glomérulos Renais/patologia , Glomérulos Renais/ultraestrutura , Pessoa de Meia-Idade , Paraproteinemias/tratamento farmacológico
6.
Kidney Blood Press Res ; 44(4): 858-869, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31352451

RESUMO

BACKGROUND/AIMS: The term monoclonal gammopathy of renal significance (MGRS) was introduced in 2012 to emphasize kidney lesions in monoclonal gammopathy patients. Bortezomib-based chemotherapy has become the first-line treatment for MGRS. OBJECTIVES: The objective of this study was to investigate whether the strategy of combining chemotherapy with autologous stem cell transplantation (ASCT) could improve prognosis and decrease functional kidney impairment in patients with MGRS. METHODS: We reported the case of a 44-year-old Asian patient who was diagnosed with MGRS and received 5 cycles of Velcade® (a trade name for bortezomib), thalidomide, and dexamethasone therapy (VTD therapy), and subsequently underwent ASCT. In addition, we performed a literature review and summarized the latest advances in the characterization, treatment, and prognosis of MGRS. RESULTS: The patient was diagnosed with light chain deposition disease by renal biopsy. After 5 cycles of VTD therapy, the patient had a very good partial response characterized by the resolution of M-protein (20.2% before treatment vs. 2.5% after treatment), remission of the level of serum free lambda (FLAM; over 80% decline), and normalization of the serum free light chain (sFLC) ratio (κ to λ). He also had a renal response characterized by a decreased serum creatinine level (1.61 vs.1.34 mg/dL) and less severe proteinuria (6.77 g/24 h vs.1.264 g/24 h) after chemotherapy. Importantly, after ASCT, the patient achieved a complete response (CR) characterized by a negative serum immunofixation electrophoresis (IFE) result and a dramatic decrement in FLAM (over 90%). Furthermore, 6 months after ASCT, the patient still remained in stable condition with a negative IFE result, normal sFLC ratio, and low level of serum creatinine (1.31 mg/dL) and proteinuria (0.339 g/24 h). In our retrospective literature analysis, we found that MGRS patient survival time and renal outcome had been markedly improved by current therapies due to the popularization of bortezomib-based chemotherapy and ASCT. CONCLUSIONS: The patient successfully achieved CR after VTD therapy followed by ASCT. However, this treatment is controversial, and a standard therapy recommendation for MGRS has not been established. Bortezomib-based chemotherapy combined with ASCT may have prospects for the treatment of MGRS, but the exact effects of ASCT remain unclear and should be thoroughly investigated.


Assuntos
Bortezomib/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Paraproteinemias/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Nefropatias/patologia , Nefropatias/terapia , Masculino , Paraproteinemias/patologia , Talidomida/uso terapêutico , Transplante Autólogo , Resultado do Tratamento
7.
Med Oncol ; 36(9): 75, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31342211

RESUMO

The use of bortezomib in the clinic has significantly improved outcomes for patients with multiple myeloma (MM), even those harboring high-risk cytogenetic abnormalities or those classified in the high-risk category according to the International Staging System (ISS). In this study, we analyzed the association between immunophenotyping on myeloma cells and the clinical outcomes of patients who received bortezomib-based regimens as first-line therapy. Immunophenotypic analysis before bortezomib therapy was performed by flow cytometry, and whether the immunophenotyping results influenced the clinical outcomes of the patients was investigated. Seventy-four newly diagnosed patients with MM were included in this study. We found that the expression of MPC-1 significantly predicted the time to next therapy (TNT), with a longer TNT in the MPC-1 positive group (p = 0.005), whereas it did not affect overall survival (OS; p = 0.773). In addition, we found that CD45-positivity was associated with shorter TNT (p = 0.0432). Following ISS assessment at treatment initiation, patients who were classified as stage I showed a slightly longer OS compared to those at stage II or III; however, these results were not significant (p = 0.0987). Furthermore, multivariate analysis revealed the prognostic significance of MPC-1 expression, as MPC-1-negativity was associated with a worse TNT. The combination of MPC-1 and CD45 status more sensibly predicted the TNT for bortezomib therapy. Our results demonstrate the clinical importance of immunophenotyping on myeloma cells to determine patient prognoses in this era of novel therapeutic agents.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imunofenotipagem , Estimativa de Kaplan-Meier , Antígenos Comuns de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
8.
Mol Med Rep ; 20(3): 2410-2418, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322176

RESUMO

The aim of the present study was to investigate the effect of bortezomib on heat shock protein 27 (HSP27) in multiple myeloma (MM) and provide a potential new target for clinical treatment. Peripheral blood was collected from 50 normal subjects and 50 patients with newly diagnosed MM and the expression of HSP27 was detected by ELISA. The changes of HSP27 after conventional vincristine, doxorubicin and dexamethasone (VAD) chemotherapy, and bortezomib plus VAD were compared. The effect of bortezomib on U266 cell proliferation and apoptosis was detected using a Cell Counting Kit­8 assay and Annexin V­FITC/propidium iodide double staining with flow cytometry. The content of HSP27 following bortezomib treatment was determined by ELISA. Western blot analysis and reverse transcription­quantitative PCR were used to detect the mRNA and protein expression of HSP27, Bax and Bcl­2. HSP27 expression was increased in patients with MM compared with healthy control subjects, and the expression was increased as the cancer progressed (P<0.05). Compared with the VAD chemotherapy group, the bortezomib plus VAD chemotherapy regimen significantly inhibited the expression of HSP27 (P<0.05), and the content of HSP27 was decreased in patients in which treatment was effective compared to those patients that exhibited disease progression (P<0.05). The efficacy of the treatment regimes was not associated with age or gender. Compared with the control group, bortezomib or OGX­427 (HSP27 inhibitor) treatment inhibited U266 cell proliferation, promoted U266 cell apoptosis (P<0.05) and significantly decreased HSP27 expression (P<0.05). Furthermore, the expression of HSP27 and Bcl­2 was significantly decreased, while the expression of Bax was increased by bortezomib and OGX­427 (P<0.05). There was no significant difference between the bortezomib and OGX­427 group in the in vitro analysis. HSP27 was positively correlated with Bcl­2 expression and negatively correlated with Bax expression in U266 cells. In conclusion, bortezomib promotes the apoptosis of MM cells, potentially by downregulating the expression of HSP27, providing a potential novel target for the clinical treatment of multiple myeloma.


Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Bortezomib/uso terapêutico , Proteínas de Choque Térmico/genética , Chaperonas Moleculares/genética , Mieloma Múltiplo/tratamento farmacológico , Antineoplásicos/farmacologia , Bortezomib/farmacologia , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Feminino , Proteínas de Choque Térmico/análise , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares/análise , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia
9.
Transplant Proc ; 51(6): 1732-1738, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31301858

RESUMO

Plasma cell-rich acute rejection (PCAR) and antibody-mediated rejection (ABMR), for which a standard treatment has not yet been established, are associated with poor graft survival after kidney transplantation. Here, we report a case series of 3 Japanese patients diagnosed with PCAR accompanied by ABMR. Steroid pulse therapy and rabbit antithymocyte globulin, plasma exchange, intravenous immunoglobulin, and rituximab therapies were sequentially performed in the first case. A graft biopsy after each treatment showed that plasma cell infiltration persisted. Five months after the initiation of rejection therapy, the patient was subjected to bortezomib therapy, which led to the partial elimination of plasma cells from the graft. However, the graft function gradually deteriorated, and hemodialysis treatment was warranted. In the other 2 cases, the patients received the same combination of therapy including bortezomib within a short period. Graft biopsies performed subsequently showed a marked decrease in the number of infiltrated plasma cells, and stabilization of renal graft function was achieved in both cases. Bortezomib, which targets plasma cells, is a potent drug that eliminates infiltrated plasma cells from the graft in PCAR. Thus, in addition to conventional therapy comprising plasma exchange, intravenous immunoglobulin, and rituximab against ABMR, bortezomib may be necessary to administer without any delay to control PCAR.


Assuntos
Bortezomib/uso terapêutico , Terapia Combinada/métodos , Rejeição de Enxerto/tratamento farmacológico , Plasmócitos/efeitos dos fármacos , Inibidores de Proteassoma/uso terapêutico , Adolescente , Corticosteroides/administração & dosagem , Pré-Escolar , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Transplante de Rim/efeitos adversos , Masculino , Plasmócitos/patologia , Plasmaferese , Estudos Retrospectivos , Rituximab/administração & dosagem , Adulto Jovem
10.
Eur J Med Chem ; 179: 791-804, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288128

RESUMO

Advances in the field of boron chemistry have expanded the application of this element in Medicinal Chemistry. Boron-containing compounds represent a new class for medicinal chemists to use in their drug designs. Bortezomib (Velcade®), a dipeptide boronic acid approved by the FDA in 2003 for treatment of multiple myeloma, paved the way for the discovery of new boron-containing compounds. After its approval, two other boron-containing compounds have been approved, tavaborole (Kerydin®) for the treatment of onychomicosis and crisaborole (Eucrisa®) for the treatment of mild to moderate atopic dermatitis. A number of boron-containing compounds have been described and evaluated for a plethora of therapeutic applications. The present review is intended to highlight the recent advances related to boron-containing compounds and their therapeutic applications. Here, we focused only in those most biologically active compounds with proven in vitro and/or in vivo efficacy in the therapeutic area published in the last years.


Assuntos
Compostos de Boro/uso terapêutico , Bortezomib/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Mieloma Múltiplo/tratamento farmacológico , Onicomicose/tratamento farmacológico , Animais , Compostos de Boro/síntese química , Compostos de Boro/química , Bortezomib/síntese química , Bortezomib/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Desenho de Drogas , Humanos
11.
Zhonghua Xue Ye Xue Za Zhi ; 40(6): 453-459, 2019 Jun 14.
Artigo em Chinês | MEDLINE | ID: mdl-31340616

RESUMO

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.


Assuntos
Bortezomib/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica , Seguimentos , Humanos , Quimioterapia de Indução , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante de Células-Tronco , Transplante Autólogo , Resultado do Tratamento
12.
Drug Des Devel Ther ; 13: 1707-1716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190749

RESUMO

Background: Administration of subcutaneous (SC) bortezomib in patients with multiple myeloma (MM) has increased in recent years. Yet, it is unclear whether there is sufficient evidence to support the use of SC bortezomib as a standard of care. Methods: A systematic review of 4 randomized controlled trials and 8 retrospective trials comparing SC to intravenous (IV) bortezomib among 1,857 MM patients was performed. Embase, PubMed, Clinical Trials.gov, Cochrane Library and reference lists were searched for relevant studies from inception until August 2018. Outcomes of interest included 1-year overall survival (OS), 1-year progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs). Random events meta-analyses were performed. We also performed sensitivity analysis to examine whether the results of the meta-analysis were robust. Results: Compared to IV administration, SC bortezomib had a significantly lower incidence of some all-grade or grade 3-4 AE, such as peripheral sensory neuropathy, leukopenia and thrombocytopenia (p<0.05). There was no statistical difference in 1-year OS, 1-year PFS, ORR between SC and IV bortezomib (p>0.05). Conclusion: The data presented so far consistently show that SC bortezomib has become a standard of care for patients with MM.


Assuntos
Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Padrão de Cuidado , Administração Intravenosa , Humanos , Injeções Subcutâneas , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
13.
Lancet ; 394(10192): 29-38, 2019 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171419

RESUMO

BACKGROUND: Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma. METHODS: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. FINDINGS: Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21-2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10-5 sensitivity threshold, assessed by multiparametric flow cytometry; both p<0·0001). Median progression-free survival from first randomisation was not reached in either group (hazard ratio 0·47, 95% CI 0·33-0·67, p<0·0001). 46 deaths on study were observed (14 vs 32, 0·43, 95% CI 0·23-0·80). The most common grade 3 or 4 adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%). INTERPRETATION: D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma. FUNDING: The Intergroupe Francophone du Myélome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Quimioterapia Adjuvante , Terapia Combinada , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/uso terapêutico , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
14.
J Clin Pharm Ther ; 44(5): 815-818, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31237703

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Hyperhaemolysis syndrome (HHS) of sickle cell anaemia (SCA) is a life-threatening condition characterized by accelerated destruction of red blood cells typically following blood transfusions. Optimal treatment strategies have not been determined; therefore, reports utilizing novel therapies are needed. CASE DESCRIPTION: A 19-year-old African American man with SCA experienced HHS following a partial red cell exchange transfusion. He was treated with methylprednisolone, rituximab, darbepoetin, Hemopure and bortezomib, with resolution of the syndrome. WHAT IS NEW AND CONCLUSION: The HHS of SCA is thought to be immune-mediated even in the absence of detectable red cell alloantibodies. New therapies, including bortezomib and Hemopure, may be useful in this syndrome.


Assuntos
Anemia Falciforme/tratamento farmacológico , Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Hemoglobinas/uso terapêutico , Hemólise/efeitos dos fármacos , Adulto , Humanos , Masculino , Adulto Jovem
15.
Eur J Haematol ; 103(3): 255-267, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31231828

RESUMO

OBJECTIVE: A post hoc analysis of two phase III trials was carried out to explore the influence of age and treatment factors on the effect of bortezomib consolidation on progression-free survival (PFS) post autologous stem cell transplantation (ASCT). METHODS: Patients with newly diagnosed multiple myeloma were assigned to one of two trials (ClinicalTrials.gov IDs: NCT00416273, NCT00416208), which were conducted in parallel, based on age (18-60 or 61-75 years, respectively). Following induction and ASCT, patients were randomized 1:1 to four 35-day cycles of bortezomib consolidation (1.6 mg/m2 IV on days 1, 8, 15, 22) or observation only. RESULTS: Median PFS with bortezomib consolidation vs observation was 33.6 vs 29.0 months (P = 0.3599) in patients aged 18-60 years (n = 202), and 33.4 vs 26.4 months (P = 0.0073) in patients aged 61-75 years (n = 155), respectively. Bortezomib consolidation post-ASCT appeared to equalize outcomes between older and younger patients who received prior treatment of differing intensity. This suggests that the effect of consolidation may be relative and may depend on the composition and intensity of induction and high-dose therapy. CONCLUSION: Older patients receiving less intensive prior treatment could experience a larger PFS benefit from bortezomib consolidation.


Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Terapia Combinada , Quimioterapia de Consolidação , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
16.
BMC Cancer ; 19(1): 504, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138244

RESUMO

BACKGROUND: Despite major advances in therapy, multiple myeloma is still an incurable malignancy in the majority of patients. To increase survival, deeper remissions (i.e. CR) translating into longer PFS need to be achieved. Incorporation of new drugs (i.e. bortezomib and lenalidomide) as induction and maintenance treatment in an intensified treatment concept, including high dose melphalan (200 mg/m2), has resulted in increased CR rates, and is considered the standard of care for younger patients. Elotuzumab in combination with lenalidomide and dexamethasone has given better results as lenalidomide and dexamethasone alone in a phase III trial. The GMMG-HD6 trial will be the first phase III trial investigating the role of elotuzumab in combination with bortezomib, lenalidomide and dexamethasone (VRD) induction/consolidation and lenalidomide maintenance within a high dose concept. METHODS: GMMG-HD6 is a randomized, open, multicenter phase III trial. The planned recruitment number is 564 NDMM patients. All patients will receive 4 VRD cycles as induction and undergo peripheral blood stem cell mobilization and harvesting. Thereafter they will be treated with high dose melphalan therapy plus autologous stem cell transplantation followed by 2 cycles of VRD consolidation and lenalidomide maintenance. Patients in arm B1 + B2 will additionally receive elotuzumab in the induction phase, whereas patients in A2 + B2 will be treated with elotuzumab added to consolidation and maintenance. The primary endpoint of the trial is PFS. Secondary objectives and endpoints are OS, CR rates after induction therapy comparing the two arms VRD (A1 + A2) vs VRD + elotuzumab (B1 + B2), CR rates after consolidation treatment, best response to treatment during the study, time to progression (TTP), duration of response (DOR), toxicity and quality of life. RESULTS: Since this is the publication of a study protocol of an ongoing study, no results can be presented. DISCUSSION: This phase III trial is designed to evaluate whether the addition of elotuzumab to an intensified treatment concept with high dose melphalan chemotherapy plus autologous stem cell transplantation and induction, consolidation and maintenance treatment with bortezomib and lenalidomide is able to improve PFS compared to the same concept without elotuzumab. TRIAL REGISTRATION: NCT02495922 on June 24th, 2015.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Lenalidomida/administração & dosagem , Melfalan/administração & dosagem , Mieloma Múltiplo/terapia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Bortezomib/uso terapêutico , Quimioterapia de Consolidação , Dexametasona/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Quimioterapia de Indução , Lenalidomida/uso terapêutico , Quimioterapia de Manutenção , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Projetos de Pesquisa , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
17.
Turk J Haematol ; 36(2): 106-111, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31046214

RESUMO

Objective: Multiple myeloma (MM) has a better survival outcome because of the development of drugs. However, equivalent outcomes cannot be expected from the same drug. Therefore, how the treatment schedule is managed is important. We analyzed VMP (bortezomib, melphalan, and prednisolone) data to determine an effective treatment strategy. Materials and Methods: We collected the data of 59 patients who were newly diagnosed with MM from January 2012 to April 2017 using electronic medical records. We analyzed baseline characteristics, responses, dose reductions, and survival. Results: The overall response rate was 86.5% [complete response (CR): 32.2%, very good partial response (VGPR): 37.3%]. The median progression-free survival was 33.6 months and the 5-year overall survival rate was 70%. There were significant better progression-free survival outcomes between CR and non-CR for each of the 4 cycles. Of the four patients who achieved CR after the first cycle, none have had disease progression as of yet. We divided patients into two groups according to the median dose (52.1 mg/m2) and we found no differences between the high-dose and low-dose groups. About 78% of patients completed 9-cycle schedules and 84% patients experienced dose reduction, mostly for reasons of non-hematologic toxicities. Conclusion: Active dose reduction helped to continue treatment and it increased the opportunity to be exposed to drugs. In the end, it resulted in improved outcome.


Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Melfalan/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Prednisona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , República da Coreia , Análise de Sobrevida , Resultado do Tratamento
18.
Amyloid ; 26(2): 66-73, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31074308

RESUMO

Background: Patients with amyloid light-chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. Currently, bortezomib is the mainstay in the treatment of AL amyloidosis, but the benefits of bortezomib in patients with ultra-high-risk (2004 Mayo stage IIIb or 2012 Mayo stage IV) AL amyloidosis have not been proved definitively. Methods: We performed a retrospective analysis of patients newly diagnosed with ultra-high-risk AL amyloidosis who received a bortezomib-based regimen or supportive treatment. We aimed to establish the effects of bortezomib on early mortality and long-term outcomes in this high-risk population. Results: Patients receiving bortezomib-containing chemotherapy (n = 62) and patients receiving no chemotherapy (n = 24) were included. Median overall survival (OS) was 30 months in the bortezomib group and 2 months in the control group (p < .001), and median progression-free survival (PFS) was 15.8 months (bortezomib) and 2 months (control; p < .001). The early-death rate (within 6 months of treatment) was 32.3% (bortezomib) and 66.7% (control; p < .001). In a landmark analysis assessing outcomes in patients surviving beyond 6 months, the 2-year OS and PFS in the bortezomib group were 77.3% and 65.8%, respectively. Conclusions: Bortezomib-based regimens can help to reduce early mortality and improve long-term survival in patients with ultra-high-risk AL amyloidosis.


Assuntos
Bortezomib/uso terapêutico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
19.
J Med Case Rep ; 13(1): 153, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31113466

RESUMO

BACKGROUND: Primary plasmacytomas are localized proliferations of clonal plasma cells occurring in the absence of a systemic plasma cell dyscrasia such as multiple myeloma. Primary plasmacytomas most commonly manifest as solitary lesions of the bone or of the upper aerodigestive tract. Presentation in a lymph node is very uncommon and can often be initially mistaken for lymphoma. Because they are local phenomena, primary plasmacytomas are managed with local therapies such as radiation or, less commonly, excision. Multifocal presentations are rare and are often not amenable to local treatment modalities, thus requiring systemic therapies. Because of their rarity, standardized treatment guidelines are not established, and treatment paradigms borrow heavily from those employed in multiple myeloma. Multifocal presentation in lymph nodes is nearly unheard of with only seven such cases reported in the existing literature, only four of which were diffuse enough to require systemic therapy. Here we describe the most diffuse and widely distributed instance of primary lymph node plasmacytoma yet reported and present a description of its successful treatment with systemic therapy. CASE PRESENTATION: A 71-year-old Asian man presented with progressive fatigue in the setting of diffuse hypermetabolic lymphadenopathy throughout his chest, abdomen, and pelvis. A diagnosis of lymphoma was initially suspected; however, a lymph node biopsy was consistent with plasmacytoma. A bone marrow biopsy was unremarkable, and no monoclonal protein was identified, establishing a diagnosis of primary extramedullary plasmacytomas of the lymph nodes. He was treated with a myeloma-like regimen consisting of four cycles of bortezomib/dexamethasone followed by two cycles of thalidomide/prednisone with improvement in symptoms and near complete resolution of prior hypermetabolic lymphadenopathy. He remains in remission over 18 months following completion of therapy. CONCLUSION: This case report and accompanying literature review highlight the exceedingly rare and easily misclassified entity of primary plasmacytoma of diffuse lymph nodes. Importantly, we demonstrate that this entity may be treated with, and demonstrate excellent response to, systemic therapies often employed in multiple myeloma.


Assuntos
Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Linfonodos/patologia , Linfadenopatia/patologia , Plasmocitoma/patologia , Prednisona/uso terapêutico , Talidomida/uso terapêutico , Idoso , Fadiga , Humanos , Linfadenopatia/tratamento farmacológico , Masculino , Plasmócitos/patologia , Plasmocitoma/tratamento farmacológico , Indução de Remissão
20.
J Clin Lab Anal ; 33(5): e22888, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31004381

RESUMO

BACKGROUND: Renal impairment (RI) is a most common complication of multiple myeloma (MM), which is associated with an increased risk of early death and worse survival. METHODS: We retrospectively analyzed clinical features and outcomes of 77 MM patients over 70 years old and compared the differences between with and without RI groups. RESULTS: The percentage of elder MM patients with RI was 61%. Hemoglobin level was a protective factor (OR = 0.954, P = 0.033), while creatinine and hypertension were hazards (OR = 1.288, P < 0.001 and OR = 30.12, P = 0.008). And the percentages of patients with mild-to-moderate RI and moderate-to-severe RI were 40.4% and 59.6%. Complete remission (CR) rate was higher in patients treated with bortezomib (33.3%) than those with non-bortezomib treatment (3.33%) (P = 0.007). Meanwhile, CRrenal was higher in patients with bortezomib (58.3%) than non-bortezomib treatment (22.2%) (P = 0.025). The median OS of the patients with RI treated with bortezomib was longer than those with non-bortezomib regimens (15.0 vs 6.0 months, P = 0.001). The same result was observed in the patients with moderate-to-severe RI (13.0 vs 6.0 months, P = 0.007). The median OS of the patients with RI receiving the bortezomib regimens (15 months) was longer than those with non-bortezomib regimens (6.0 months) (P = 0.001). CONCLUSION: Hemoglobin is a protective factor in elder patients with RI, while creatinine and hypertension were hazards. The median OS of elderly patients with RI was worse, and bortezomib can improve the CR rate in these patients.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Insuficiência Renal/etiologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Hemoglobinas/análise , Humanos , Hipertensão/etiologia , Masculino , Mieloma Múltiplo/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
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