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1.
Lancet Haematol ; 8(4): e299-e304, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33770485

RESUMO

To our knowledge, no study has evaluated the quality of control groups in randomised controlled trials of multiple myeloma. We aimed to do a systematic review of randomised controlled trials of multiple myeloma to ascertain the quality of the control groups used. PubMed (MEDLINE), Embase, Cochrane Controlled Register of Trials, and CinicalTrials.gov were searched for articles of randomised controlled trials of multiple myeloma based in the USA that initiated participant enrolment between Jan 1, 2010, and June 30, 2020. A control group regimen was considered to be inferior if a previous randomised controlled trial had shown an improved progression-free survival versus the control group before enrolment. Of 49 identified randomised controlled trials, seven (14%) began enrolling patients into inferior control groups after an existing superior regimen to the control had already been published. Nine (18%) of the 49 trials continued enrolment on substandard control groups after data emerged during the study enrolment period. The median time that newer data emerged regarding inferiority of the control group from the time a trial first enrolled a patient was 13 months (IQR 8-29 months). 12 (75%) of these 16 randomised controlled trials are published, and nine (75%) of the 12 published trials had overlapping investigators with trials that had previously shown the inferiority of the control group being used. Greater scrutiny on the quality of control groups in randomised controlled trials of multiple myeloma is needed.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Grupos Controle , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Mieloma Múltiplo/epidemiologia , Intervalo Livre de Progressão , Controle de Qualidade , Indução de Remissão/métodos , Estados Unidos/epidemiologia
2.
Ann Hematol ; 100(4): 995-1002, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33651193

RESUMO

Waldenstrom macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma with great heterogeneity, and the data of peripheral blood T-lymphocyte subsets in WM are limited. This study aimed to investigate the clinical correlation and distribution of circulating T-lymphocyte subsets in newly diagnosed WM patients. We retrospectively searched medical records for 86 newly diagnosed WM patients. Comparisons of the absolute CD3+ T-lymphocyte count (ACD3C), CD4+ T-lymphocyte count (ACD4C), CD8+ T-lymphocyte count (ACD8C), and CD4+/CD8+ T-lymphocyte ratio (CD4+/CD8+) as continuous parameters in different groups were calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Young patients (<65 years) had lower ACD8C levels and a higher CD4+/CD8+ ratio. And the lower level of ß2-microglobulin (<3 mg/L) was associated with a higher CD4+/CD8+ ratio. With a median follow-up of 25 months, the univariate survival analysis showed that CD4+/CD8+ ratio inversion (CD4+/CD8+<1.5) was associated with shorter OS and PFS, and multivariate analysis confirmed that inverted CD4+/CD8+ ratio could be an independent adverse prognostic factor for OS and PFS. Additionally, initial treatment with rituximab or bortezomib significantly improved the PFS and OS of CD4+/CD8+ inversion patients but did not affect normal CD4+/CD8+ patients. We show that low circulating CD4+/CD8+ ratio at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy which included rituximab or bortezomib significantly improved PFS and OS for patients with CD4+/CD8+ ratio less than 1.5.


Assuntos
Relação CD4-CD8 , Macroglobulinemia de Waldenstrom/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/mortalidade , Microglobulina beta-2/análise
3.
Ann Hematol ; 100(4): 1059-1063, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33528611

RESUMO

Daratumumab (DARA) is a human IgG-K monoclonal antibody (MoAb) targeting CD38 that is approved alone or in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone for relapsed or refractory MM (RRMM) in patients previously exposed or double refractory to proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs). However, there are limited data on its clinical activity and tolerability in real-world patients. Therefore, in the present study, we aim to determine the efficacy and toxicity profile of daratumumab in a real-life setting. In this study, we report the experience of the multiple myeloma GIMEMA Lazio Group in 62 relapsed/refractory MM patients treated with daratumumab as monotherapy who had previously received at least two treatment lines including a PI and an IMiDs or had been double refractory. Patients received DARA 16 mg/kg intravenously weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks until disease progression or unacceptable toxicity. The overall response rate to daratumumab was 46%. Median progression-free survival (PFS) and overall survival reached 2.7 and 22.4 months, respectively. DARA was generally well tolerated; however, 2 patients interrupted their therapy due to adverse events. Present real-life experience confirms that DARA monotherapy is an effective strategy for heavily pre-treated and refractory patients with multiple myeloma, with a favorable safety profile.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Proteínas do Mieloma/análise , Oligopeptídeos/administração & dosagem , Intervalo Livre de Progressão , Talidomida/administração & dosagem , Talidomida/análogos & derivados
4.
Am J Hematol ; 96(3): 367-378, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33393136

RESUMO

The introduction of novel agents over the last decade has rapidly expanded the therapeutic landscape of multiple myeloma (MM) for both transplant-eligible and transplant-ineligible patients. The assessment of minimal residual disease (MRD) by next-generation flow cytometry or next-generation sequencing is established as a powerful predictor of long-term outcomes. The use of MRD in response-adapted clinical trials may provide opportunities to identify candidates for treatment escalation and de-escalation. Agents with proven activity in the relapsed and refractory setting are being studied in the management of high-risk newly diagnosed MM (NDMM). Here, we summarize the most recent clinical trials that have led to the current paradigms in the management of NDMM. We also discuss how novel agents could be incorporated in the newly diagnosed setting and potential clinical trial designs that could leverage MRD information with the goal of treatment optimization.


Assuntos
Mieloma Múltiplo/terapia , Terapias em Estudo , Corticosteroides/administração & dosagem , Corticosteroides/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Bortezomib/administração & dosagem , Bortezomib/farmacologia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Gerenciamento Clínico , Drogas em Investigação/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Humanos , Fatores Imunológicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Neoplasia Residual , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacologia , Inibidores de Proteases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Talidomida/administração & dosagem , Talidomida/farmacologia
5.
Ann Hematol ; 100(3): 725-734, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33432438

RESUMO

Multiple myeloma (MM) is an incurable disease, and patients usually receive multiple lines of therapy. Due to the abundance of novel treatments for MM, we conducted a network meta-analysis to identify combinations that could fare better than others in relapsed/refractory MM, in the setting of novel drugs. We searched PubMed and Cochrane databases for phase III trials in previously treated MM that had lenalidomide or bortezomib in the control arm. The primary endpoint was progression-free survival (PFS), extracted as hazard-ratio. We used the P score to rank treatments. Thirteen studies were included. All but two studies compared one novel agent against two, with or without dexamethasone. Based on the P score, daratumumab and pegylated liposomal doxorubicin had a higher probability of achieving better PFS, followed by isatuximab, carfilzomib, pomalidomide, and panobinostat. Although most overall survival data were not mature enough, the addition of a second or third novel agent to either immunomodulatory (IMID) or proteasome inhibitor (PI) backbone seemed to improve survival (HR = 0.84, 95CI 0.77-0.92). Severe adverse events were more frequent with isatuximab, panobinostat, and pomalidomide. In summary, in the absence of trials directly comparing two novel agents-based therapies, we provide a tool that indirectly compares these newer therapies and that can help physicians to prioritize some regimens over others.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Lenalidomida/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bortezomib/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/patologia , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Metanálise em Rede , Intervalo Livre de Progressão , Recidiva
6.
BMJ Case Rep ; 14(1)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504531

RESUMO

Acquired von Willebrand syndrome is a rare bleeding disorder characterised by a later age of onset without a personal or family history of bleeding diathesis. It is vital to discern acquired von Willebrand syndrome from inherited von Willebrand disease and other acquired bleeding disorders as management differs significantly. Acquired von Willebrand syndrome is usually secondary to an underlying disorder such as lymphoproliferative disorder, myeloproliferative neoplasm, solid tumour, cardiovascular disorder, autoimmune disorders or hypothyroidism. Diagnosis is often delayed with a significant risk of morbidity and even mortality. Here we present a case of a 74-year-old man with an acquired bleeding disorder and work up suggestive of acquired von Willebrand syndrome secondary to immunoglobulin G kappa multiple myeloma. He was treated successfully with intravenous immunoglobulin, von Willebrand Factor/Coagulation Factor VIII Complex (human), myeloma directed chemotherapy and autologous stem cell transplantation. We also discuss the management strategies that are largely based on retrospective studies and case reports.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/complicações , Transplante de Células-Tronco , Doenças de von Willebrand/etiologia , Idoso , Bortezomib/administração & dosagem , Angiografia por Tomografia Computadorizada , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Erros de Diagnóstico , Combinação de Medicamentos , Embolização Terapêutica , Fator VIII/uso terapêutico , Hemofilia A/diagnóstico , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Nefropatias/etiologia , Nefropatias/terapia , Masculino , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Transplante Autólogo , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/tratamento farmacológico , Fator de von Willebrand/uso terapêutico
7.
Leuk Res ; 101: 106498, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33453475

RESUMO

BACKGROUND: Multiple myeloma (MM) patients presenting with anaemia as their sole clinical manifestation are rare and not fully defined. METHODS: Retrospective multi-site study comparing the characteristics and outcome of MM patients with anaemia only with matched patients, presenting with multi-organ disease. RESULTS: Anaemia-only patients had a higher percentage of bone marrow monoclonal plasma cells group (median 60% [IQR 42-80%] vs. 37% [IQR 17-65%], respectively; p < 0.001), and a lower responsiveness to treatment (≥VGPR rates were 54% vs 74%, p = 0.049). Median survival in anaemia only patients was 65.9 ± 6.9 vs 83.4 ± 8.8 months in matched control patients (P = n.s). CONCLUSIONS: MM patients presenting with anaemia only represents a unique, potentially less favorable population.


Assuntos
Anemia , Bortezomib/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/mortalidade , Anemia/terapia , Autoenxertos , Bortezomib/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Estudos Retrospectivos
8.
Am J Hematol ; 96(3): 330-337, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33326116

RESUMO

Induction therapy for multiple myeloma with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (d) (VRd) was traditionally administered as bortezomib given twice weekly on a 3 week cycle. A modified schedule of weekly bortezomib has been adopted over time to decrease treatment burden for patients and reduce treatment-emergent neuropathy. This study evaluates the response rates and outcomes with different schedules of bortezomib in VRd administered for first-line treatment for patients with newly diagnosed MM (NDMM). We retrospectively analyzed patients treated with upfront VRd from June 30th 2008 to December 31st 2018, for variations of bortezomib administration. Five hundred and fifty-five (555) NDMM patients met inclusion criteria; median age 63 years and 61% men. Bortezomib was administered twice weekly every 21 days in 43%, once weekly every 21 days in 41% and once weekly every 28 days in 16%. Though peripheral sensory neuropathy was more frequent with twice weekly dosing (P = .002), this group achieved shorter time to best response (P = .01). Weekly every 21-day treatment saw higher VGPR or better rates (P = .02). However, with median follow up time of 37 months (IQR 22-56), we found no difference in PFS or OS among the groups. While small differences in response rates were found among the varying administration schedules of bortezomib administration, there was no significant effect on PFS or OS. Given that VRd remains a first line standard of care option for newly diagnosed MM, in the absence of a large trial comparing bortezomib dosing schedule modifications, these results are helpful in supporting current practices of once weekly administration.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Vias de Administração de Medicamentos , Esquema de Medicação , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
9.
Lancet Haematol ; 8(1): e45-e54, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357482

RESUMO

BACKGROUND: The introduction of immunomodulatory agents, proteasome inhibitors, and autologous haematopoietic stem-cell transplantation has improved outcomes for patients with multiple myeloma, but patients with high-risk multiple myeloma have a poor long-term prognosis. We aimed to address optimal treatment for these patients. METHODS: SWOG-1211 is a randomised phase 2 trial comparing eight cycles of lenalidomide (25 mg orally on days 1-14 every 21 days), bortezomib (1·3 mg/m2 subcutaneously on days 1, 4, 8, and 11 every 21 days), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12 every 21 days; RVd) induction followed by dose-attenuated RVd maintenance (bortezomib 1 mg/m2 subcutaneously on days 1, 8, and 15; lenalidomide 15 mg orally on days 1-21; dexamethasone 12 mg orally on days 1, 18, and 15 every 28 days) until disease progression with or without elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1-2, on days 1 and 11 for cycles 3-8, and on days 1 and 15 during maintenance). Patients were randomly assigned (1:1) to either RVd or RVd-elotuzumab. High-risk multiple myeloma was defined by one of the following: gene expression profiling high risk (GEPhi), t(14;16), t(14;20), del(17p) or amp1q21, primary plasma cell leukaemia and elevated serum lactate dehydrogenase (two times the upper limit of normal or more). The primary endpoint was progression-free survival, and all analyses were done on intention-to-treat basis among eligible patients who were evaluable for response. This study is registered with ClinicalTrials.gov, NCT01668719. FINDINGS: 100 (RVd n=52, RVd-elotuzumab n=48) patients were enrolled between Oct 27, 2013, and May 15, 2016, across 26 cooperative group institutions in the USA. Median age was 64 years (IQR 57-70, range 36-85). 74 (75%) of 99 had International Staging System stage II or stage III disease, 47 (47%) of 99 had amp1q21, 37 (37%) of 100 had del17p, 11 (11%) of 100 had t(14;16), eight (9%) of 90 were GEPhi, seven (7%) of 100 had primary plasma cell leukaemia, five (5%) of 100 had t(14;20), four (4%) of 100 had elevated serum lactate dehydrogenase, and 17 (17%) had two or more features. With a median follow-up of 53 months (IQR 46-59), no difference in median progression-free survival was observed (RVd 33·64 months [95% CI 19·55-not reached], RVd-elotuzumab 31·47 months [18·56-53·98]; hazard ratio 0·968 [80% CI 0·697-1·344]; one-sided p=0·45]. 37 (71%) of 52 patients in the RVd group and 37 (77%) of 48 in the RVd-elotuzumab group had grade 3 or worse adverse events. No significant differences in the safety profile were observed, although some notable results included grade 3-5 infections (four [8%] of 52 in the RVd group, eight [17%] of 48 in the RVd-elotuzumab group), sensory neuropathy (four [8%] of 52 in the RVd group, six [13%] of 48 in the RVd-elotuzumab group), and motor neuropathy (one [2%] of 52 in the RVd group, four [8%] of 48 in the RVd-elotuzumab group). There were no treatment-related deaths in the RVd group and one death in the RVd-elotuzumab group for which study treatment was listed as possibly contributing by the investigator. INTERPRETATION: In the first randomised study of high-risk multiple myeloma reported to date, the addition of elotuzumab to RVd induction and maintenance did not improve patient outcomes. However, progression-free survival in both study groups exceeded the original statistical assumptions and supports the role for continuous proteasome inhibitors and immunomodulatory drug combination maintenance therapy for this patient population. FUNDING: National Institutes of Health, National Cancer Institute, Bristol Myers Squibb, Celgene, Leukemia and Lymphoma Society.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Taxa de Sobrevida
10.
N Z Med J ; 133(1527): 104-110, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33332332

RESUMO

Multiple myeloma is the second most common blood cancer in New Zealand with higher incidence in Maori and Pacific Island populations. It remains an incurable disease but the rapidly changing treatment landscape has led to improved outcome. In response to recent changes in funding of anti-myeloma therapy in New Zealand, the New Zealand Myeloma Interest Group has reviewed the latest literature and updated the treatment pathway of transplant-eligible patients with newly diagnosed multiple myeloma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Quimioterapia de Consolidação , Quimioterapia de Indução , Quimioterapia de Manutenção , Mieloma Múltiplo/terapia , Transplante de Medula Óssea/métodos , Bortezomib/administração & dosagem , Consenso , Quimioterapia de Consolidação/métodos , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Quimioterapia de Indução/métodos , Lenalidomida , Nova Zelândia , Guias de Prática Clínica como Assunto , Talidomida/administração & dosagem
11.
Int J Hematol ; 112(6): 835-840, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32876851

RESUMO

Hematopoietic stem and progenitor cell (HSPC) mobilization regimens in multiple myeloma typically use filgrastim (GCSF) alone or combination of GCSF with plerixafor or high-dose cyclophosphamide. Murine model and human studies have shown HSPC mobilization potential of bortezomib. A total of 37 patients underwent mobilization using bortezomib 1.3 mg/m2 on day 1, 4, 8 and 11, cyclophosphamide 1 g/m2 on day 8 and 9, and GCSF 10 µg/kg from day 10 (B-Cy-GCSF). This regimen was compared with our earlier cohort of patients where cyclophosphamide was given at dose of 1 g/m2 on day 1 and day 2 followed by GCSF 10 µg/kg from day 4 (Cy-GCSF). In B-Cy-GCSF group, median CD34 cells collected were 9.21 × 106/kg (range 4.95-17.1) while in the Cy-GCSF cohort, the median CD34 cell yield was 8.2 × 106/kg (0.4-24.2). Target CD34 cells yield of 5 × 106/kg was achieved with single apheresis in 58.6% of patients after B-Cy-GCSF mobilization as compared to 44.3% in Cy-GCSF group (p = 0.07). Three patients failed mobilization after Cy-GCSF, while no patients failed mobilization in bortezomib group. Addition of bortezomib to Cy-GCSF mobilization showed a trend towards increased CD34 collection and reduced need for apheresis sessions.


Assuntos
Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Antígenos CD34/metabolismo , Remoção de Componentes Sanguíneos , Feminino , Filgrastim/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade
12.
Medicine (Baltimore) ; 99(28): e20961, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664099

RESUMO

BACKGROUND: Chemotherapy with or without consolidation followed by autologous hematopoietic stem cell transplantation is the first-line treatment for mantle cell lymphoma. However, the effectiveness and safety of bortezomib-based chemotherapy for patients with mantle cell lymphoma is still uncertain. METHODS: In this systematic review, the electronic databases of Cochrane Central Register of Controlled Trials, EMBASE, and PUBMED will be searched from inception to May 1, 2020. Randomized controlled trials that assessed the effectiveness and safety of bortezomib in combination with chemotherapy for patients with mantle cell lymphoma will be included. The patient's important outcomes include overall survival, progression-free survival, overall response rate, quality of life, and serious adverse events (eg, grade III-IV peripheral neuropathy, neutropenia, and infection). All process of the study selection, data extraction, and methodology evaluation will be carried out by 2 authors independently. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will provide a detailed summary of latest evidence related to the effectiveness and safety of bortezomib in combination with chemotherapy in overall survival, progression-free survival, overall response rate, quality of life, and serious adverse events for patients with mantle cell lymphoma CONCLUSION:: The findings of this study may provide possible guidance for bortezomib in combination with chemotherapy for patients with mantle cell lymphoma. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD 42020154938.


Assuntos
Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Linfoma de Célula do Manto/tratamento farmacológico , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/efeitos adversos , Humanos , Resultado do Tratamento
14.
Int J Hematol ; 112(6): 860-863, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32710430

RESUMO

A 71-year-old petite Japanese woman was diagnosed with IgG λ-type multiple myeloma with acute kidney injury, severe anemia, and a pathological rib fracture. Emergent hemodialysis was initiated combined with chemotherapy including bortezomib, lenalidomide, and pomalidomide, but myeloma had become refractory due to the treatments. Therefore, a combination therapy with weekly daratumumab (16 mg/kg), bortezomib (0.7 mg/m2), and dexamethasone was started. Daratumumab was administered on a non-dialysis day with a reduced infusion speed to avoid acute water load. No infusion-related adverse events were observed throughout the treatment. Daratumumab and bortezomib were administrated weekly for three times in the first cycle and a hematological very good partial response was achieved. Then, the treatment schedule was reduced to once every three weeks from the 2nd cycle, the very good partial response had been maintained. Fourteen months after the initiation of maintenance hemodialysis, the patient was able to reduce dialysis frequency due to improvement of renal function. A modified daratumumab, bortezomib and dexamethasone regimen could be a valuable treatment option for dialysis-dependent myeloma patients.


Assuntos
Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Anticorpos Monoclonais/administração & dosagem , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Esquema de Medicação , Mieloma Múltiplo/complicações , Diálise Renal , Idoso , Quimioterapia Combinada , Feminino , Humanos , Mieloma Múltiplo/imunologia , Resultado do Tratamento
15.
Ann Hematol ; 99(8): 1735-1740, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32535708

RESUMO

To explore the clinical characteristics and outcomes in Chinese patients with type I cryoglobulinemia (CG), we retrospectively analyzed the clinical data, management, and outcomes of 45 patients diagnosed with type I CG in our hospital from January 2015 to March 2019. In our study, all type I CGs were secondary to hematologic diseases, and monoclonal gammopathy of unknown significance was the most common primary disease, accounting for 48.9% (n = 22). Additionally, B cell non-Hodgkin lymphoma, Waldenström's macroglobulinemia, and multiple myeloma accounted for 24.4% (n = 11), 20.0% (n = 9), and 6.7% (n = 3), respectively. In patients with type I CG, skin damage was the most common symptom, presenting in 57.8% of the patients, followed by peripheral neuropathy (22.2%) and renal involvement (15.6%). Treatment was initiated in 29 patients (64.4%), and the most common choice was a rituximab-based regimen in 13 patients (44.8%), followed by bortezomib-based regimen in 11 patients (37.9%). Clinical symptoms were significantly improved after treatment, and the clinical remission rate was 86.2%, including 34.5% of complete clinical remission, while the laboratory response rate was 88.9%, including 33.3% of complete response and 55.6% of partial response. The expected 1-year overall survival was 97.8%. In conclusion, for patients with multisystemic involvement, such as skin damage, kidney damage, or peripheral neuropathy, the diagnosis of type I CG should be considered, and the underlying disease needs to be explored. Symptoms and primary diseases should be taken into consideration before choosing initial management.


Assuntos
Bortezomib/administração & dosagem , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/mortalidade , Rituximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Crioglobulinemia/sangue , Crioglobulinemia/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
16.
Hematol Oncol ; 38(4): 517-522, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32569436

RESUMO

Multiple myeloma has extremely heterogeneous outcomes. Among prognostic factors, t(4;14) and del(17p) are rare oncogenic events associated with very poor prognosis. In an exploratory case-control study, we compared the combination of Busulfan-Melphalan or TBI-Melphalan with high dose Melphalan as a conditioning regimen in a series of 48 patients with del(17p) or t(4;14). These regimens were preceded by a Bortezomib-containing induction. Progression-free survival (PFS) was the primary endpoint whereas overall survival (OS) and complete response (CR) rate were the secondary endpoints. Twenty consecutive cases of high-risk myeloma received a reinforced conditioning regimen of Busulfan 0.8 mg/kg x4/j IV from day-6 to day-3 pre- graft (BuMel) or total body irradiation (TBI) 12 Gy (TbiMel), having received Melphalan 140 mg/m2 at day-2 pre-graft. These cases were matched to 28 controls treated with Melphalan 200 mg/m2 at day-2 (Mel200). After intensification ± consolidation, with a median follow-up of 6.3 years, the CR rate was higher in the BuMel/TbiMel group (65% vs 50%, P = .006). No differences were observed between both groups in terms of PFS and OS (P = .96). PFS in patients with a del(17p) mutation tended to be superior in the BuMel/TbiMel group. Our exploratory study shows that reinforcing the intensification regimen with Busulfan or TBI does not seem to improve the prognosis associated to t(4;14) and del(17p) abnormalities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante/mortalidade , Irradiação Corporal Total/mortalidade , Bortezomib/administração & dosagem , Bussulfano/administração & dosagem , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo
17.
Lancet Haematol ; 7(6): e456-e468, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32359506

RESUMO

BACKGROUND: The emergence of highly active novel agents has led some to question the role of autologous haematopoietic stem-cell transplantation (HSCT) and subsequent consolidation therapy in newly diagnosed multiple myeloma. We therefore compared autologous HSCT with bortezomib-melphalan-prednisone (VMP) as intensification therapy, and bortezomib-lenalidomide-dexamethasone (VRD) consolidation therapy with no consolidation. METHODS: In this randomised, open-label, phase 3 study we recruited previously untreated patients with multiple myeloma at 172 academic and community practice centres of the European Myeloma Network. Eligible patients were aged 18-65 years, had symptomatic multiple myeloma stage 1-3 according to the International Staging System (ISS), measurable disease (serum M protein >10 g/L or urine M protein >200 mg in 24 h or abnormal free light chain [FLC] ratio with involved FLC >100 mg/L, or proven plasmacytoma by biopsy), and WHO performance status grade 0-2 (grade 3 was allowed if secondary to myeloma). Patients were first randomly assigned (1:1) to receive either four 42-day cycles of bortezomib (1·3 mg/m2 administered intravenously or subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) combined with melphalan (9 mg/m2 administered orally on days 1-4) and prednisone (60 mg/m2 administered orally on days 1-4) or autologous HSCT after high-dose melphalan (200 mg/m2), stratified by site and ISS disease stage. In centres with a double HSCT policy, the first randomisation (1:1:1) was to VMP or single or double HSCT. Afterwards, a second randomisation assigned patients to receive two 28-day cycles of consolidation therapy with bortezomib (1·3 mg/m2 either intravenously or subcutaneously on days 1, 4, 8, and 11), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12) or no consolidation; both groups received lenalidomide maintenance therapy (10 mg orally on days 1-21 of a 28-day cycle). The primary outcomes were progression-free survival from the first and second randomisations, analysed in the intention-to-treat population, which included all patients who underwent each randomisation. All patients who received at least one dose of study drugs were included in the safety analyses. This study is registered with the EU Clinical Trials Register (EudraCT 2009-017903-28) and ClinicalTrials.gov (NCT01208766), and has completed recruitment. FINDINGS: Between Feb 25, 2011, and April 3, 2014, 1503 patients were enrolled. 1197 patients were eligible for the first randomisation, of whom 702 were assigned to autologous HSCT and 495 to VMP; 877 patients who were eligible for the first randomisation underwent the second randomisation to VRD consolidation (n=449) or no consolidation (n=428). The data cutoff date for the current analysis was Nov 26, 2018. At a median follow-up of 60·3 months (IQR 52·2-67·6), median progression-free survival was significantly improved with autologous HSCT compared with VMP (56·7 months [95% CI 49·3-64·5] vs 41·9 months [37·5-46·9]; hazard ratio [HR] 0·73, 0·62-0·85; p=0·0001). For the second randomisation, the number of events of progression or death at data cutoff was lower than that preplanned for the final analysis; therefore, the results from the second protocol-specified interim analysis, when 66% of events were reached, are reported (data cutoff Jan 18, 2018). At a median follow-up of 42·1 months (IQR 32·3-49·2), consolidation therapy with VRD significantly improved median progression-free survival compared with no consolidation (58·9 months [54·0-not estimable] vs 45·5 months [39·5-58·4]; HR 0·77, 0·63-0·95; p=0·014). The most common grade ≥3 adverse events in the autologous HSCT group compared to the VMP group included neutropenia (513 [79%] of 652 patients vs 137 [29%] of 472 patients), thrombocytopenia (541 [83%] vs 74 [16%]), gastrointestinal disorders (80 [12%] vs 25 [5%]), and infections (192 [30%] vs 18 [4%]). 239 (34%) of 702 patients in the autologous HSCT group and 135 (27%) of 495 in the VMP group had at least one serious adverse event. Infection was the most common serious adverse event in each of the treatment groups (206 [56%] of 368 and 70 [37%] of 189). 38 (12%) of 311 deaths from first randomisation were likely to be treatment related: 26 (68%) in the autologous HSCT group and 12 (32%) in the VMP group, most frequently due to infections (eight [21%]), cardiac events (six [16%]), and second primary malignancies (20 [53%]). INTERPRETATION: This study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. FUNDING: Janssen and Celgene.


Assuntos
Quimioterapia de Consolidação/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Transplante Autólogo/métodos , Administração Intravenosa , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Infecções/induzido quimicamente , Infecções/epidemiologia , Injeções Subcutâneas , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Proteínas do Mieloma/análise , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Plasmocitoma/patologia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Transplante Autólogo/mortalidade
18.
Am J Med Sci ; 360(2): 206-207, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32387118

Assuntos
Fraturas por Compressão/etiologia , Fraturas Espontâneas/etiologia , Plasmocitoma/complicações , Fraturas da Coluna Vertebral/etiologia , Neoplasias da Coluna Vertebral/complicações , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Descompressão Cirúrgica , Dexametasona/administração & dosagem , Progressão da Doença , Feminino , Fraturas por Compressão/diagnóstico por imagem , Fraturas Espontâneas/diagnóstico por imagem , Humanos , Fraturas do Úmero/etiologia , Fraturas do Úmero/cirurgia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Laminectomia , Lenalidomida/administração & dosagem , Mieloma Múltiplo/sangue , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/tratamento farmacológico , Plasmocitoma/diagnóstico por imagem , Plasmocitoma/patologia , Plasmocitoma/cirurgia , Tomografia por Emissão de Pósitrons , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X
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