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1.
Haematologica ; 109(7): 2219-2228, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38356463

RESUMO

The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase II study, selinexor, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexamethasone (DVd), for the treatment of relapsed and refractory multiple myeloma (RRMM). The aim of the trial was to assess the efficacy and safety of the combination of selinexor with DVd (S-DVd). A total of 57 patients were enrolled in the two parts of the study. Part 1 enrolled a heavily pretreated population with at least three prior lines (PL) of therapy and part 2 enrolled an early relapse population with at least one PL of therapy. The primary endpoint was complete response (CR) rate in part 2 and overall response rate (ORR) in part 1. In the latter, 24 patients were treated with a median of three PL. Overall response rate (ORR) was 50% with two CR. Median progression- free survival (PFS) was 7 months. In part 2, 33 patients were enrolled, with a median of one PL. ORR was 82% and CR or better was 33%. Median PFS was 24 months. In lenalidomide-refractory patients, a median PFS of 22.1 months was observed. Thrombocytopenia was the most common hematological adverse event (69%; grade 3-4: 34%) and nausea, the most frequent non-hematological adverse event (38%; grade 3-4: 6%). Sixty-two percent of the patients required dose modifications. In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable safety profile representing a potential option for the treatment of RRMM patients.


Assuntos
Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Hidrazinas , Mieloma Múltiplo , Triazóis , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Triazóis/administração & dosagem , Triazóis/uso terapêutico , Triazóis/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Hidrazinas/administração & dosagem , Hidrazinas/uso terapêutico , Hidrazinas/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Idoso de 80 Anos ou mais , Adulto , Resultado do Tratamento , Resistencia a Medicamentos Antineoplásicos , Recidiva
2.
Haematologica ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38988266

RESUMO

The value of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify the M-protein is being investigated in patients with monoclonal gammopathies but no data are yet available in high-risk smoldering myeloma (HRsMM). We have therefore investigated QIP-MS to monitor peripheral residual disease (PRD) in 62 HRsMM patients enrolled in the GEM-CESAR trial. After 24 cycles of maintenance, detecting the M-protein by MS or clonal plasma cells by NGF identified cases with a significantly shorter median PFS (mPFS; MS: not reached vs 1,4 years, p=0.001; NGF: not reached vs 2 years, p=0.0002) but reaching CR+sCR did not discriminate patients with different outcome. With NGF as a reference, the combined results of NGF and MS showed a high negative predictive value (NPV) of MS: 81% overall and 73% at treatment completion. When sequential results were considered, sustained negativity by MS or NGF was associated with a very favorable outcome with a mPFS not yet reached vs 1.66 years and 2.18 years in cases never attaining PRD or minimal residual disease (MRD) negativity, respectively. We can thus conclude that 1) the standard response categories of the IMWG do not seem to be useful for treatment monitoring in HRsMM patients, 2) MS could be used as a non-invasive, clinical valuable tool with the capacity of guiding timely bone marrow evaluations (based on its high NPV with NGF as a reference) and 3) similarly to NGF, sequential results of MS are able identify a subgroup of HRsMM patients with long-term disease control. This study was registered at www.clinicaltrials.gov (ClinicalTrials.gov identifier: NCT02415413).

3.
Qual Life Res ; 24(4): 979-92, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25281010

RESUMO

PURPOSE: We studied the validity and responsiveness of an item response theory (IRT) scoring method for assessing major depressive episode (MDE) and generalized anxiety disorder (GAD) severity based on direct assessment of DSM-IV-TR symptoms. METHODS: Prospective cohort study (baseline, 1-month, 3-months assessments) of patients seeking help for incident or aggravated mood or anxiety symptoms from primary, outpatient and inpatient mental health centers (N = 244; 67.81 % active cases - 100 % under psychiatric treatment). The drop-out rate at 3 months was 24.89 %. Patients were assessed at each follow-up for presence/absence of DSM-IV symptoms of MDE (nine symptoms) and GAD (eight symptoms). IRT scores for depression (INS-D) and anxiety (INS-G), based on response patterns, were obtained by means of a 2-parameter model. Diagnostic accuracy was assessed with receiver operating characteristic analysis, using a blinded MINI interview as gold standard. Scores' construct validity was compared with external clinician-administered (Hamilton Depression Rating Scale, HRSD; Hamilton Anxiety Rating Scale, HAM-A) and self-reported severity measures (PHQ-9; Beck Anxiety Inventory-Subjective Aspects, BAI-Sub). Responsiveness was analyzed based on the evolution of HRSD and HAM-A scores. RESULTS: Both severity scores showed excellent reliability (INS-D: 0.92; INS-G: 0.93) and yielded high diagnostic accuracy (INS-D: AUC = 0.96; INS-G: AUC = 0.91) with respect to MINI diagnoses. INS-D and INS-G had higher correlations with clinician-administered measures of the same disorder (INS-D-HRSD: 0.73; INS-G-HAM-A: 0.53) than with self-reported measures (INS-D-PHQ-9: 0.69; INS-G-BAI-Sub: 0.49). Patients who recovered during follow-up showed important decreases in severity (Cohen's d INS-D:-1.38; INS-G: -1.75). About 90 % variance of INS-D and INS-G score changes over time was associated with changes in clinical status. CONCLUSIONS: INS-D and INS-G are short reliable, valid, and responsive measures that can be used for diagnostic and severity assessment of mood and anxiety disorders in outpatient care.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Escalas de Graduação Psiquiátrica , Adulto , Idoso , Transtornos de Ansiedade/psicologia , Estudos de Coortes , Transtorno Depressivo Maior/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Qualidade de Vida , Curva ROC , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
4.
Early Hum Dev ; 88(8): 669-75, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22381046

RESUMO

BACKGROUND: Neonatal brain injuries are the main cause of visual deficit produced by damage to posterior visual pathways. While there are several studies of visual function in low-risk preterm infants or older children with brain injuries, research in children of early age is lacking. AIM: To assess several aspects of visual function in preterm infants with brain injuries and to compare them with another group of low-risk preterm infants of the same age. STUDY DESIGN AND SUBJECTS: Forty-eight preterm infants with brain injuries and 56 low-risk preterm infants. OUTCOME MEASURES: The ML Leonhardt Battery of Optotypes was used to assess visual functions. This test was previously validated at a post-menstrual age of 40 weeks in newborns and at 30-plus weeks in preterm infants. RESULTS: The group of preterm infants with brain lesions showed a delayed pattern of visual functions in alertness, fixation, visual attention and tracking behavior compared to infants in the healthy preterm group. The differences between both groups, in the visual behaviors analyzed were around 30%. These visual functions could be identified from the first weeks of life. CONCLUSION: Our results confirm the importance of using a straightforward screening test with preterm infants in order to assess altered visual function, especially in infants with brain injuries. The findings also highlight the need to provide visual stimulation very early on in life.


Assuntos
Lesões Encefálicas/epidemiologia , Doenças do Prematuro/epidemiologia , Transtornos da Visão/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Testes Visuais
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