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1.
Artigo em Inglês | MEDLINE | ID: mdl-33939911

RESUMO

Objective: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. Methods: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 × 106 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). Results: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/- 0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. Conclusion: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of ß-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.

2.
Lancet Oncol ; 22(3): e105-e118, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33662288

RESUMO

This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.


Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Terapia de Salvação , Humanos , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-32967807

RESUMO

INTRODUCTION: Daratumumab is a CD38-targeting monoclonal antibody with established efficacy and safety in patients with relapsed or refractory multiple myeloma (RRMM). We report results of an early access protocol (EAP) of daratumumab monotherapy for RRMM in a cohort of Brazilian patients. METHODS: Patients with RRMM and ≥3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or who were double refractory to both a PI and IMiD received daratumumab, 16 mg/kg, intravenously weekly for 8 weeks, biweekly for 16 weeks, and every 4 weeks thereafter until disease progression, unacceptable toxicity, loss of clinical benefit, or study conclusion or if daratumumab became available with reimbursement. RESULTS: Forty-nine patients received ≥1 dose of daratumumab. The median (range) duration of treatment was 6.4 (0.3-11.8) months, with a median (range) of 8 (1-13) treatment cycles. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 38.8% of patients, most frequently neutropenia and pneumonia (10.2% each). Seven (14.3%) patients discontinued treatment due to TEAEs; 3 patients discontinued due to daratumumab-related TEAEs. Serious TEAEs occurred in 38.8% of patients. Infusion-related reactions were reported in 25 (51.0%) patients, were primarily grade 1/2, and the majority (23 patients) occurred during the first infusion. Twenty (40.8%) patients achieved a partial response or better; median progression-free survival was 8.25 (95% confidence interval, 5.55-17.54) months. CONCLUSION: In this EAP, daratumumab monotherapy in Brazilian patients showed a safety and efficacy profile consistent with clinical studies of daratumumab monotherapy in patients with heavily pretreated RRMM. ClinicalTrials.gov identifier: NCT02477891.

4.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(3): 200-205, July-Sept. 2020.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1134043

RESUMO

ABSTRACT Since the World has been facing the COVID-19 pandemic, special attention has been taken concerning cancer patients; related to their immunosuppression status, adding risk for more aggressive COVID-19 and mortality, but also concerns about the access and the quality of care in cancer therapy. The COVID-19 pandemic impacts the number of infected, its related mortality, as well as the care of cancer patients. Multiple myeloma patients are a particular group with several important aspects to be considered during pandemic times. In essence, they are immunosuppressed in different intensities during their treatment. Most of them are elderly and all of them require long-term therapy, with prolonged contact with the health care system, possibly including a stem cell transplant during the treatment. A panel of experts in multiple myeloma and infectious diseases discusses pieces of evidence and the lack of the same in the scenario of COVID-19 in myeloma patients, while also exposing what is expected for the next phases of the COVID-19 pandemic.

5.
Leukemia ; 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32778736

RESUMO

Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

6.
Front Immunol ; 11: 993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582156

RESUMO

Objective: To evaluate the short term safety and potential therapeutic effect of allogenic adipose tissue-derived stromal/stem cells (ASCs) + cholecalciferol in patients with recent-onset T1D. Methods: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 106 cells/kg) and cholecalciferol 2000 UI/day for 3 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide (CP), insulin dose, HbA1c, time in range (TIR), glucose variability (continuous glucose monitoring) and frequency of CD4+FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3). Results: 13 patients were included (8: group 1; 5: group 2). Their mean age and disease duration were 26.7 ± 6.1 years and 2.9 ± 1.05 months. Adverse events were transient headache (n = 8), mild local reactions (n = 7), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), mild floaters (n = 2), central retinal vein occlusion (n = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; p = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; p = 0.03) than group 2. In group 1, 2 patients became insulin free (for 4 and 8 weeks) and all were in honeymoon at T3 (vs. none in group 2; p = 0.01). CP variations did not differ between groups (-4.6 ± 29.1% vs. +2.3 ± 59.65%; p = 0.83). Conclusions: Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D. ClinicalTrials.gov registration: NCT03920397.

7.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(2): 118-124, Apr.-June 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1134012

RESUMO

ABSTRACT Background: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. Methods: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. Results: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p = 0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. Conclusion: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

9.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(2): 166-172, Apr.-June 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1134025

RESUMO

ABSTRACT Objective: To describe the oral health status of patients with multiple myeloma and compare to a control group. Materials and methods: The medical history of the studied subjects was obtained from the medical records and through interviews. Trained examiners evaluated the oral mucosa, teeth, periodontium and imaging aspects. The dental status was evaluated by the decayed, missing and filled teeth index. The presence of bone lesions was investigated with cone beam computer tomography images of the jaws. Results: The most common oral mucosa features were paleness (31%) and coated tongue (14.3%) in the multiple myeloma group (N = 42); and coated (21.4%) and fissured tongue (10.7%) in the control group (N = 28). The mean DMFT index of patients with multiple myeloma was high, but not significantly different from controls (14.57 versus 19.69, p = 0.975). Hypodense lesions suggestive of multiple myeloma were observed in the jaws of 73.8% of the patients. Hypodense lesions related to teeth were detected in 33.3% of the patients and in 53.6% of the controls (p = 0.832). Conclusions: The studied population of multiple myeloma patients presented many oral health issues that needed attention. Thus, oral care should be included in the routine treatment to improve the quality of the oral status in these patients.

10.
Hematol Transfus Cell Ther ; 42(3): 200-205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32405620

RESUMO

Since the World has been facing the COVID-19 pandemic, special attention has been taken concerning cancer patients; related to their immunosuppression status, adding risk for more aggressive COVID-19 and mortality, but also concerns about the access and the quality of care in cancer therapy. The COVID-19 pandemic impacts the number of infected, its related mortality, as well as the care of cancer patients. Multiple myeloma patients are a particular group with several important aspects to be considered during pandemic times. In essence, they are immunosuppressed in different intensities during their treatment. Most of them are elderly and all of them require long-term therapy, with prolonged contact with the health care system, possibly including a stem cell transplant during the treatment. A panel of experts in multiple myeloma and infectious diseases discusses pieces of evidence and the lack of the same in the scenario of COVID-19 in myeloma patients, while also exposing what is expected for the next phases of the COVID-19 pandemic.

12.
Hematol Transfus Cell Ther ; 42(2): 166-172, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31582338

RESUMO

OBJECTIVE: To describe the oral health status of patients with multiple myeloma and compare to a control group. MATERIALS AND METHODS: The medical history of the studied subjects was obtained from the medical records and through interviews. Trained examiners evaluated the oral mucosa, teeth, periodontium and imaging aspects. The dental status was evaluated by the decayed, missing and filled teeth index. The presence of bone lesions was investigated with cone beam computer tomography images of the jaws. RESULTS: The most common oral mucosa features were paleness (31%) and coated tongue (14.3%) in the multiple myeloma group (N=42); and coated (21.4%) and fissured tongue (10.7%) in the control group (N=28). The mean DMFT index of patients with multiple myeloma was high, but not significantly different from controls (14.57 versus 19.69, p=0.975). Hypodense lesions suggestive of multiple myeloma were observed in the jaws of 73.8% of the patients. Hypodense lesions related to teeth were detected in 33.3% of the patients and in 53.6% of the controls (p=0.832). CONCLUSIONS: The studied population of multiple myeloma patients presented many oral health issues that needed attention. Thus, oral care should be included in the routine treatment to improve the quality of the oral status in these patients.

13.
Dentomaxillofac Radiol ; 49(2): 20190155, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31670576

RESUMO

OBJECTIVES: To verify quantitative differences of the mandibular cortical and trabecular bone between patients with multiple myeloma (MM) under bisphosphonate (BP) therapy and a control group never exposed to BP. METHODS: Clinical and demographic characteristics were collected through medical records and interviews. Mandibular cortical thickness (MCT) and fractal dimension (FD) were measured on cone beam computed tomography (CBCT) images, on the molar region, in both groups. Additionally, FD was measured on periapical digital intraoral radiography and results were compared to CBCT measurements. RESULTS: There were 33 patients with MM under BP therapy and 28 controls, with no significant differences in gender and age between groups. Pamidronate was used by all MM patients, either associated or not to other types of BP. The median MCT was higher in MM group exposed to BP (5.20 mm) than in controls (3.50 mm, p < 0.001). There were no significant differences in the median FD between patients in the MM group and controls, on CBCT (0.95 vs 0.90, p = 0.814) and periapical digital intraoral radiography (0.98 vs 0.96, p = 0.963), respectively, even when more than one type of BP was used. CONCLUSIONS: The MCT represents an useful tool in the detection of bone dimensional changes caused by BP, in patients with MM. Additional studies are necessary to improve the knowledge on the quantitative evaluation of trabecular jaw bone, in individuals with MM, under BP therapy.


Assuntos
Conservadores da Densidade Óssea , Difosfonatos , Mandíbula , Mieloma Múltiplo , Conservadores da Densidade Óssea/uso terapêutico , Tomografia Computadorizada de Feixe Cônico , Difosfonatos/uso terapêutico , Humanos , Arcada Osseodentária/diagnóstico por imagem , Arcada Osseodentária/efeitos dos fármacos , Mandíbula/diagnóstico por imagem , Mandíbula/efeitos dos fármacos , Mieloma Múltiplo/complicações , Radiografia Dentária Digital
14.
Hematol Transfus Cell Ther ; 42(2): 118-124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31537476

RESUMO

BACKGROUND: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. METHODS: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. RESULTS: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p=0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. CONCLUSION: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

15.
Oral Radiol ; 36(2): 168-176, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31222625

RESUMO

PURPOSE: To establish an evaluation protocol for the identification and description of the variations in multiple myeloma (MM) lesions of the jaws, by means of cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Tomography exams from 33 MM patients were evaluated in this retrospective observational study. The reconstructions were analyzed simultaneously, according to the established protocol, with the following description criteria: anatomic location, size, margins, inner aspect, relationship with adjacent structures, and presence or absence of a punched-out aspect. The exams were further subdivided into groups of patients using, or not bisphosphonates. RESULTS: There were osteolytic lesions in 100% of cases, most of which were extended to more than one anatomical region. Poorly defined margins were more frequent in the maxilla than in the mandible. Extensive bone resorption presenting multilocular areas was the most frequently observed aspect, being 86.2% for maxilla and 87.9% for mandible. In relation to bisphosphonates, patients who used the medication had more poorly defined bone margins and contortions (68.6%) than those who did not undergo drug therapy (31.4%). No well-defined lesions were observed (p = 0.34%). CONCLUSION: It was possible to establish a protocol for evaluation of MM lesions in CBCT images and to identify that when evaluated three-dimensional, lesions tend to be poorly defined and have no pattern of description, as described in two-dimensional "punched-out".


Assuntos
Mieloma Múltiplo , Tomografia Computadorizada de Feixe Cônico , Humanos , Mandíbula/diagnóstico por imagem , Maxila , Mieloma Múltiplo/diagnóstico por imagem , Estudos Retrospectivos
18.
Arq Neuropsiquiatr ; 77(3): 166-173, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30970129

RESUMO

It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). OBJECTIVE: We examined the impact of CIITA polymorphisms -168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. METHODS: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). RESULTS: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA -168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA -168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA -168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. CONCLUSION: These data suggest that CIITA -168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.


Assuntos
Progressão da Doença , Esclerose Múltipla/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único/genética , Transativadores/genética , Adolescente , Adulto , Idoso , Avaliação da Deficiência , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Acetato de Glatiramer/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
19.
Arq. neuropsiquiatr ; 77(3): 166-173, Mar. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001345

RESUMO

ABSTRACT It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). Objective: We examined the impact of CIITA polymorphisms −168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. Methods: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). Results: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA −168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA −168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA −168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. Conclusion: These data suggest that CIITA −168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.


RESUMO Atualmente não se sabe como os fatores genéticos podem influenciar o curso clínico da esclerose múltipla (EM). Objetivo: Examinamos o impacto dos polimorfismos CIITA −168A/G (rs3087456) e CIITA +1614G/C (rs4774) no risco de progressão da incapacidade, gravidade e resposta aos tratamentos imunomoduladores de primeira linha. Métodos: O DNA genômico foi extraído de amostras de sangue. Utilizamos o software ABI3730xl e GeneMapper v.4.0 (Applied Biosystems) para identificar variações genotípicas. Todos os pacientes foram acompanhados e reavaliados clinicamente em intervalos de três meses. A progressão da incapacidade foi medida pela EDSS e a gravidade da doença pelo MSSS. Resultados: Incluímos 37 homens e 80 mulheres. Não encontramos evidências sobre a influência dos SNPs estudados no EDSS e na resposta terapêutica aos fármacos avaliados. Realizamos uma análise de regressão logística com o MSSS e observamos uma evolução menos grave da EM associada aos tipos selvagens CIITA −168AA e CIITA +1614GG, pois a chance do paciente atingir MSSS2 e MSSS3 diminuiu em 61%/75%, e 66/75% respectivamente (p < 0,0001). Embora menos significativo, o CIITA +1614GC também foi relacionado com evolução menos grave da EM e a chance do paciente atingir o MSSS3 diminuiu 79% (p = 0,015). Nós também observamos que o genótipo CIITA −168GG foi mais frequente no MSSS2 e MSSS3 e teve uma razão de chance 40% menor para atingir forma mais grave da EM. Conclusão: Estes dados sugerem que os polimorfismos CIITA −168AA, CIITA +1614GG e CIITA +1614GC podem estar associados a um melhor curso clínico da EM. Este conhecimento pode ser útil para uma melhor compreensão da EM e o seu manejo terapêutico.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Proteínas Nucleares/genética , Transativadores/genética , Progressão da Doença , Polimorfismo de Nucleotídeo Único/genética , Esclerose Múltipla/genética , Fatores de Tempo , Índice de Gravidade de Doença , Modelos Logísticos , Estudos Retrospectivos , Interferon beta/uso terapêutico , Avaliação da Deficiência , Estimativa de Kaplan-Meier , Estudos de Associação Genética , Acetato de Glatiramer/uso terapêutico , Frequência do Gene , Genótipo , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/mortalidade , Esclerose Múltipla/tratamento farmacológico
20.
Hematol., Transfus. Cell Ther. (Impr.) ; 41(1): 76-83, Jan.-Mar. 2019. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1002040

RESUMO

Abstract The treatment of patients with relapsed and/or refractory multiple myeloma has improved considerably in the last 15 years, after the introduction of proteasome inhibitors and immunomodulatory drugs. The first clinical trials with new proteasome inhibitors have produced exciting results, particularly those comparing triplet regimens with standard doublet regimens, with a gain in progression-free survival accompanied by an acceptable safety profile and either similar or better health-related quality of life. New proteasome inhibitors hold the potential to fill unmet needs in multiple myeloma management regarding improvement of clinical outcomes, including delayed progression of disease in high-risk patients. This review summarizes the main pharmacological properties and clinical outcomes of these agents, and discusses their potential to change the whole multiple myeloma therapeutic landscape.

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