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BACKGROUND: Treating multiple myeloma is complex, and providing supportive care through an interdisciplinary approach is essential. AIM: To report and synthesize pharmacists' clinical activities and impact on the care of patients with multiple myeloma. METHOD: This was a scoping review that followed the PRISMA-ScR reporting recommendations. A search was conducted in PubMed, Embase, Web of Science, Scopus, and LILACS from the inception of the database until January 10th, 2024. Papers that reported pharmacists' clinical activities in the care of patients with multiple myeloma were included. Descriptive Elements of Pharmacist Intervention Characterization Tool (DEPICT) version 2 was used to characterize the pharmacists' clinical activities. The results are presented as a narrative and tabular synthesis. RESULTS: A total of 2885 records were identified, 10 of which met the inclusion criteria. Pharmacists' clinical activities related to 'direct patient care' (n = 8) and 'medication counseling, education, and training' (n = 7) were the most cited. Most were provided for patients (n = 8), by one-on-one contact (n = 9), and through face-to-face communication method (n = 8), with patient counseling being the main action taken by pharmacists (n = 7). Materials that supported pharmacists' actions were cited in five studies. Integrating pharmacists into interdisciplinary teams led to improved process, clinical, humanistic, and economic outcomes. CONCLUSION: This scoping review emphasizes pharmacists' clinical activities in improving the care of patients with multiple myeloma. There is a need to develop studies with patient-reported outcomes and comprehensive reporting of pharmacists' clinical activities to ensure reproducibility and effective implementation in clinical practice.
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Adequate stem cell harvesting is required for autologous hematopoietic transplantation. In deficient mobilizer patients, the collection of stem cells can be challenging because of the impossibility of achieving satisfactory CD34 cell counts with GCSF + - chemotherapy. Plerixafor is a potent and expensive drug that promotes the release of stem cells from the medullary niche to the peripheral blood and allows satisfactory harvests. We performed a retrospective analysis of 370 patients with myeloma and lymphoma harvested at our institution. 99 % of patients achieved satisfactory apheresis using Plerixafor in 45 %. Satisfactory harvests were obtained in patients mobilized with GCSF or plerixafor. In patients who used plerixafor, it was necessary to perform fewer apheresis procedures (P = 0.05). In multivariate analysis, the only factor that predicted the need for plerixafor was the presence of less than 30,000 CD34 / ul on the day of apheresis (OR 0.3. p < 0.001). Since we adopted the plerixafor protocol guided by CD34 counts, the number of patients with harvest failure has decreased. In conclusion, the rational and standardized use of plerixafor favors satisfactory harvest in patients who require autologous transplantation in South-American patients.
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Remoção de Componentes Sanguíneos , Transplante Autólogo , Humanos , Feminino , Masculino , Remoção de Componentes Sanguíneos/métodos , Pessoa de Meia-Idade , Transplante Autólogo/métodos , Adulto , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/métodos , Chile , Idoso , Ciclamos/farmacologia , Ciclamos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , BenzilaminasRESUMO
Non-secretory multiple myeloma (NSMM) is a rare cancer of plasma cells characterized by the absence of detectable monoclonal M protein in the blood or urine. A 57-year-old woman presented with mandibular pain but without intraoral swelling. Imaging studies revealed multiple osteolytic lesions in her mandible and pronounced root resorption of the left mandibular second molar. Biopsy results showed atypical plasmacytoid cells positive for anti-kappa, CD138, MUM1, and CD79a antibodies, but negative for anti-lambda and CD20. These results were indicative of a malignant plasma cell neoplasm. No abnormalities were revealed by free light chain assay or by serum or urine protein electrophoresis, leading to a diagnosis of NSMM. The patient began chemotherapy in conjunction with bisphosphonate therapy and achieved remission following treatment. This case underscores the critical role of dentists in the early detection and prevention of NSMM complications, as the disease can initially present in the oral cavity.
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Histone methyltransferases (HMTs) are enzymes that regulate histone methylation and play an important role in controlling transcription by altering the chromatin structure. Aberrant activation of HMTs has been widely reported in certain types of neoplastic cells. Among them, G9a/EHMT2 and GLP/EHMT1 are crucial for H3K9 methylation, and their dysregulation has been associated with tumor initiation and progression in different types of cancer. More recently, it has been shown that G9a and GLP appear to play a critical role in several lymphoid hematologic malignancies. Importantly, the key roles played by both enzymes in various diseases made them attractive targets for drug development. In fact, in recent years, several groups have tried to develop small molecule inhibitors targeting their epigenetic activities as potential anticancer therapeutic tools. In this review, we discuss the physiological role of GLP and G9a, their oncogenic functions in hematologic malignancies of the lymphoid lineage, and the therapeutic potential of epigenetic drugs targeting G9a/GLP for cancer treatment.
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INTRODUCTION: Triple- and quad-refractory multiple myeloma patients usually have an aggressive course and a poor prognosis. Available therapeutic options are scarce. METHODS: The objective of the current study was to evaluate responses and toxicities of VDTPACE or mCBAD with hematopoietic stem-cell support as a bridge to subsequent therapies in patients with refractory/relapsed multiple myeloma. RESULTS: Thirteen patients were included (11 mCBAD, 2 VDTPACE), and 21 cycles of chemotherapy with hematopoietic stem-cell support were delivered. Mean number of previous therapies was 4.8. Stem cells were infused on a median day 9.9 after chemotherapy. Mean time to neutrophil recovery was 18.2 days in patients receiving the first cycle and 15.9 following subsequent cycles. Before therapy, most patients were in PD (77%), PR (15%), or VGPR (8%). Following treatment, the best responses achieved were PR (46%), VGPR (46%), and CR (8%). Median overall and progression-free survivals were 17 and 9 months. There has been no case of non-relapse mortality. In the 21 cycles, the main complications were infectious. CONCLUSION: Intensive chemotherapy can decrease disease burden in patients with relapsed/refractory MM, and stem-cell support can successfully decrease toxicities and treatment-related mortality associated with these regimens and may be a good bridging option.
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French Guiana is a French Overseas territory with singular features: it has a high prevalence of HIV and HTLV-1, its population is ethnically mixed, with widespread poverty, and up to 20% of the population lives in geographic isolation. In this context, we used registry data to estimate incidence and mortality due to hematological malignancies and to compare them with France and tropical Latin America. ICD codes C90 and C88 were compiled between 2005 and 2014. The direct standardization of age structure was performed using the world population. Survival analysis was performed, and Kaplan-Meier curves were drawn. The overall standardized incidence rate was 32.9 per 100,000 male years and 24.5 per 100,000 female years. Between 2005 and 2009, the standardized incidence rate was 29.6 per 100,000 among men and 23.6 per 100,000 among women, and between 2010 and 2014, it was 35.6 per 100,000 among men and 25.2 per 100,000 among women. Multiple myeloma/plasmocytoma and mature t/NK cell lymphomas, notably adult t-cell lymphoma/leukemia due to HTLV-1 infection, were the two most common hematologic malignancies and causes of death. Non-Hodgkin's lymphoma incidence estimates were greater than global estimates. After adjusting for age, sex, and type of malignancy, people born in a foreign country independently had a poorer case-fatality rate, presumably reflecting difficulties in accessing care. The epidemiology of hematological malignancies in French Guiana has features that distinguish it from mainland France or from Latin America. The incidence of multiple myeloma and adult t-cell lymphoma/leukemia was significantly greater in French Guiana than in France or other Latin American countries.
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Objetivo: Analisar o uso de medicamentos potencialmente inapropriados (MPIs) e o uso de medicamentos usados em terapia de suporte que requerem cautela em idosos com câncer (MTSRCICs), determinando os fatores associados. Visou-se também determinar a concordância entre os critérios explícitos empregados na identificação de MPI. Metodologia: Estudo transversal com indivíduos com mieloma múltiplo (MM), idade ≥ 60 anos em tratamento ambulatorial. Os MPI foram identificados de acordo com os critérios AGS Beers 2019, PRISCUS 2.0 e o Consenso Brasileiro de Medicamentos Potencialmente Inapropriados (CBMPI). Os MTSRCIC foram definidos de acordo com a National Comprehensive Cancer Network. Os fatores associados ao uso de MPI e MTSRCIC foram identificados por regressão logística múltipla. O grau de concordância entre os três critérios explícitos empregados no estudo foi mensurado pelo coeficiente kappa Cohen. Resultados: As frequências de MPI foram 52,29% (AGS Beers 2019), 62,74% (CBMPI), 65,36% (PRISCUS 2.0) e 52,29% (MTSRCICs). As concordâncias entre AGS Beers 2019 com PRISCUS 2,0 e com CBMPI foram altas, enquanto a concordância entre CBMPI e PRISCUS 2.0 foi excelente. No modelo final de regressão logística polifarmácia foi associada positivamente ao uso de MPI por idosos para os três critérios explícitos utilizados, além de associado à utilização de MTSRCICs. Conclusões: A frequência do uso de MPI e de MTSRCIC foi elevada. A concordância em relação ao uso de MPI entre os critérios AGS Beers 2019, CBMPI e PRISCUS 2.0 foi alta ou excelente. A polifarmácia apresentou associação independente e positiva com uso de MPIs e de MTSRCICs por pacientes idosos com MM. (AU)
Objectives: To analyze the use of potentially inappropriate medications (PIMs) and medications used in supportive therapy that require caution in older adults with cancer, in addition to determining associated factors the agreement between criteria sets used to identify PIMs. Methods: This cross-sectional study included individuals with multiple myeloma aged ≥ 60 years who were undergoing outpatient treatment. PIMs were identified according to American Geriatric Society Beers 2019, PRISCUS 2.0, and Brazilian Consensus on Potentially Inappropriate Medicines criteria. Medications of concern were defined according to National Comprehensive Cancer Network criteria. Factors associated with the use of PIMs and medications of concern were identified using multiple logistic regression. The degree of agreement between the 3 criteria sets was measured using Cohen's kappa coefficient. Results: The frequency of PIM use was 52.29% according to American Geriatric Society Beers criteria, 62.74% according to Brazilian Consensus criteria, and 65.36% according to PRISCUS criteria, while 52.29% of the patients were using medications of concern. Agreement between American Geriatric Society Beers, PRISCUS, and Brazilian Consensus criteria was high, while it was excellent between Brazilian Consensus and PRISCUS criteria. In the final logistic regression model, polypharmacy was associated with PIM use according to each criteria set, as well as the use of medications of concern. Conclusions: The frequency of PIMs and medications of concern was high. Agreement about PIM use between the American Geriatric Society Beers, Brazilian Consensus, and PRISCUS criteria was high or excellent. There was an independent association between polypharmacy and the use of PIMs and medications of concern by older patients with multiple myeloma. (AU)
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Humanos , Idoso , Idoso de 80 Anos ou mais , Prescrição Inadequada , Mieloma MúltiploRESUMO
Although multiple myeloma (MM) is a neoplasm that leads affected individuals to death, little is known about why some patients survive much longer than others. In this context, we investigated the transcriptomic profile of bone marrow hematopoietic stem cells obtained from MM patients and compared the clinical outcomes of death and survival six months after bone marrow transplantation. The leukapheresis products of 39 patients with MM eligible for autologous transplantation were collected and analyzed. After extraction, the RNA was analyzed using the GeneChip Human Exon 1.0 Array method. The transcriptome profile was analyzed in silico, and the differentially expressed signaling pathways of interest were validated. The results showed a difference in the expression of inflammation-related genes, immune response processes, and the oxidative stress pathway. The in silico study also pointed out the involvement of the NFκB transcription factor in the possible modulation of these genes. We chose to validate molecules participating in these processes, including the cytokines TNF-α, IFN-γ, and TGF-ß1; in addition, we measured the levels of oxidative stress mediators (pro-oxidant profile and the total antioxidant capacity). TNF-α levels were significantly reduced in patients who died and were over 50 years old at diagnosis, as well as in patients with plasmacytoma. Increased TNF-α was detected in patients with very high levels of ß2-microglobulin. IFN-γ reduction was observed in patients with a complete response to treatment compared to those with a very good response. Patients with plasmacytoma who died also had an increased pro-oxidant profile. These data show the profile of inflammatory response markers that are altered in patients with MM who die quickly and serve as a basis for the development of future studies of markers to predict better survival in this disease.
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Mediadores da Inflamação , Mieloma Múltiplo , Transcriptoma , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/metabolismo , Pessoa de Meia-Idade , Masculino , Feminino , Transcriptoma/genética , Mediadores da Inflamação/metabolismo , Idoso , Estresse Oxidativo , Adulto , Células da Medula Óssea/metabolismo , Análise de Sobrevida , NF-kappa B/metabolismo , Inflamação/metabolismo , Inflamação/genética , Perfilação da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progression-free survival (HR 0.52; 95% CI 0.43-0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63-0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26-1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02-1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38-2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13-1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms.
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Multiple myeloma (MM) is an incurable hematological cancer requiring multiple lines of anti-myeloma regimens to promote disease remission and increase patient survival. The study assessed the incidence and reasons for discontinuation of first-line therapy in outpatients who started MM therapy in Belo Horizonte, Brazil from 2009 to 2020. A historical cohort study in which patients were followed from treatment initiation until discontinuation of first-line therapy. Discontinuation of first-line therapy was characterized as (i) discontinuation followed by a second-line therapy, and (ii) discontinuation that prevented patients from receiving a subsequent line of treatment. Non-parametric competing risk analysis with a 95% confidence interval estimated the cumulative incidences of discontinuation followed by a second-line therapy. The probability of discontinuation was compared according to selected variables using the Gray's test at a significance level of 5%. Approximately half of the participants (n = 260) were female and younger than 65 years. Discontinuation of first-line therapy followed by a second-line therapy accounted for 50.4% of the patients and occurred up to 30th month. The main reason for discontinuation not qualifying patients for receiving second-line therapy was to achieve a response to treatment. The maximum times for discontinuation not followed by a second-line therapy ranged from 12 to 20 months due to deaths or response to treatment. The probability of receiving second-line therapy was higher among patients initiating therapy in 2009-2014 and those not undergoing transplantation. In conclusion, discontinuation of first-line therapy followed by second-line treatment occurred as likely as the discontinuation not followed by a subsequent line.