Managing patients with multiple myeloma during the COVID-19 pandemic: recommendations from an expert panel - ABHH monoclonal gammopathies committe

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.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation

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.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation.

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.

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.

BCL-2 as therapeutic target for hematological malignancies.

Disruption of the physiologic balance between cell proliferation and cell death is an important step of cancer development. Increased resistance to apoptosis is a key oncogenic mechanism in several hematological malignancies and, in many cases, especially in lymphoid neoplasias, has been attributed to the upregulation of BCL-2. The BCL-2 protein is the founding member of the BCL-2 family of apoptosis regulators and was the first apoptosis modulator to be associated with cancer. The recognition of the important role played by BCL-2 for cancer development and resistance to treatment made it a relevant target for therapy for many diseases, including solid tumors and hematological neoplasias. Among the different strategies that have been developed to inhibit BCL-2, BH3-mimetics have emerged as a novel class of compounds with favorable results in different clinical settings, including chronic lymphocytic leukemia (CLL). In April 2016, the first inhibitor of BCL-2, venetoclax, was approved by the US Food and Drug Administration for the treatment of patients with CLL who have 17p deletion and had received at least one prior therapy. This review focuses on the relevance of BCL-2 for apoptosis modulation at the mitochondrial level, its potential as therapeutic target for hematological malignancies, and the results obtained with selective inhibitors belonging to the BH3-mimetics, especially venetoclax used in monotherapy or in combination with other agents.

Development and implementation of a comprehensive psychosocial screening program in a Brazilian cancer center.

OBJECTIVE: International guidelines recommend routine screening for distress as part of care practices. Accordingly, a Brazilian cancer center developed and implemented a distress screening program (DS) in 2007, which was enhanced in 2009 through the inclusion of a psychosocial care meeting group (DS + PCM) regarding patients' psychosocial needs. The current paper will provide an overview of the development and pilot implementation of this program and initial analyses to assess patient outcomes and report initial results to extend international research on this key aspect of cancer care. METHOD: Patients were assessed for distress, anxiety and depression, and in the DS+PCM phase for quality of life at the first day of chemotherapy infusion, at midpoint, and at treatment end. We compared data from program phases (DS vs DS + PCM), with a sequential cohort design and mixed effects modeling. RESULTS: Clinical and demographic characteristics were similar between groups. Patients receiving DS + PCM showed significantly lower distress and depression/anxiety upon chemotherapy initiation (Ps < .001). While both groups reported significantly lowered distress and total depression/anxiety scores across time (Ps < .003), patients receiving DS + PCM maintained the lowest distress and total anxiety/depression at all assessments. Patients from DS + PCM group also reported improvements in quality of life over time. CONCLUSIONS: The current study provides preliminary evidence that a multidisciplinary structured screening program utilizing validated measures and team meetings is associated with reduced impairment in patients' psychological well being. This program provided more opportunities for collaboration among providers with increased multidisciplinary meetings, enabled patients to more easily report problems, and ensured rapid access to relevant resources.