Unmet needs in multiple myeloma in Brazil from physicians' perspective ­ barriers in quality of life and disease management / Necessidades não atendidas em mieloma múltiplo no Brasil sob a perspectiva de médicos ­ barreiras na qualidade de vida e manejo da doença

Objective: There is an increasing trend of the overall survival rates of multiple myeloma (MM) patients over the years, increasing the necessity to improve their quality of life and attenuate unmet medical needs. Therefore, this study aims to explore and describe unmet medical needs and barriers in Brazilian MM patients, based on physicians' perspective. Methods: A questionnaire with 41 questions was developed to collect information regarding clinical characteristics, unmet medical needs and barriers for the diagnosis and treatment of MM in Brazil. After physicians' responses, a panel discussion with all the participants was had in order to collect additional data and validate physicians' responses. Results: Participants had a mean of 18 years of professional experience and attended to mean of thirty MM patients per month. MM patients treated by these physicians had a median time of disease of 7.5 months when initiating treatment in the public sector, and 2.5 months in the private sector. In both systems, the majority of patients referred were from general practitioners. Peripheral neuropathy was the most common adverse event reported with higher impact on patients' adherence and QoL. Conclusion: There are several challenges as to unmet medical needs, especially when comparing the private and public healthcare systems in Brazil. According to physicians, providing access to basic diagnostic procedures and adopting educational measures for both physicians and patients would help to minimize barriers in the current scenario of MM management in Brazil.

Objetivo: Existe uma tendência no aumento das taxas de sobrevida global de pacientes de mieloma múltiplo (MM) ao longo dos anos, aumentando a necessidade de melhorar sua qualidade de vida e atenuar as necessidades médicas não atendidas na área. Desta forma, o objetivo deste estudo explorar e descrever as necessidades médicas não atendidas e as barreiras em pacientes brasileiros de MM, a partir da perspectiva de médicos. Métodos: Um questionário com 41 questões foi desenvolvido para coletar dados sobre as características clínicas, necessidades médicas não atendidas e barreiras no diagnóstico e tratamento de MM no Brasil. Depois de coletar a resposta dos médicos, uma discussão em forma de painel com todos os participantes foi realizada para coletar dados adicionais validar as respostas do questionário. Resultados: Os participantes tinham, em média, 18 anos de experiência profissional, atendendo-se no total uma média de 30 pacientes de MM por mês. Os pacientes de MM atendidos por esses médicos no sistema público apresentam em média 7,5 meses de doença ao iniciar o tratamento, enquanto no sistema privado apresentavam 2,5 meses. Em ambos os sistemas, a maioria dos pacientes foi referenciada por clínicos gerais. Neuropatia periférica foi o evento adverso mais frequentemente reportado pelos médicos, com maior impacto na adesão ao tratamento e na qualidade de vida. Conclusão: Existem diversos desafios relativos às necessidades médicas não atendidas, especialmente ao comparar os sistemas público e privado no Brasil. De acordo com os participantes, o acesso aos procedimentos diagnósticos básicos e a adoção de medidas de educação médica e de pacientes minimizariam as barreiras importantes no cenário brasileiro atual.

Multiple myeloma cell lines and primary tumors proteoma: protein biosynthesis and immune system as potential therapeutic targets.

Despite great advance in multiple myeloma (MM) treatment since 2000s, it is still an incurable disease and novel therapies are welcome. Therefore, the purpose of this study was to explore MM plasma cells' (MM-PC) proteome, in comparison with their normal counterparts (derived from palatine tonsils of normal donors, ND-PC), in order to find potential therapeutic targets expressed on the surface of these cells. We also aimed to evaluate the proteome of MM cell lines with different genetic alterations, to confirm findings obtained with primary tumor cells. Bone marrow (BM) samples from eight new cases of MM and palatine tonsils from seven unmatched controls were submitted to PC separation and, in addition to two MM cell lines (U266, RPMI-8226), were submitted to protein extraction for mass spectrometry analyses. A total of 81 proteins were differentially expressed between MM-PC and ND-PC - 72 upregulated and nine downregulated; U266 vs. RPMI 8226 cell lines presented 61 differentially expressed proteins - 51 upregulated and 10 downregulated. On primary tumors, bioinformatics analyses highlighted upregulation of protein biosynthesis machinery, as well as downregulation of immune response components, such as MHC class I and II, and complement receptors. We also provided comprehensive information about U266 and RPMI-8226 cell lines' proteome and could confirm some patients' findings.

FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells.

INTRODUCTION: Multiple myeloma (MM) development involves a series of genetic abnormalities and changes in the bone marrow (BM) microenvironment, favoring the growth of the tumor and failure of local immune control. T regulatory (Treg) cells play an important role in dampening anti-tumor immune responses while T-helper-17 (Th17) cells seem to be critical for the eradication of malignant cells. The aim of our study was to characterize the expression of Treg- and Th17-related genes in total myeloma BM samples to assess their role as biomarkers, prognostic factors, and possible therapeutic targets in this incurable disease. METHODS: Expression of markers for Treg (FOXP3, CTLA4) and Th17 cells (RORγt) was determined by quantitative real-time PCR in BM aspirates of 46 MM patients, four patients with monoclonal gammopathy of undetermined significance, five solitary plasmacytomas, and five healthy BM donors. Gene expression was evaluated regarding an influence on the patients' overall survival (OS). RESULTS: FOXP3 and CTLA4 presented a sixfold (p = 0.02) and 30-fold higher expression (p = 0.03), respectively, in MM patients than in controls. RORγt expression was similar in MM patients and controls. Median OS of MM patients was 16.8 (range 4.5-29.1) months, and international staging system was the only independent prognostic factor for patients survival. CONCLUSIONS: Overexpression of FOXP3 and CTLA4 in total BM samples suggests a local accumulation of immunosuppressive Tregs, the MM tumor environment, possibly dampening anti-tumor host immune responses. Therapeutic approaches targeting Treg cells and restoring local anti-tumor immunity may provide new treatment strategies for this incurable malignancy.