Incidence of thromboembolism and associated factors in multiple myeloma patients treated with immunomodulatory drugs: a retrospective analysis in Belo Horizonte, Brazil.

PURPOSE: The use of immunomodulators in the treatment of multiple myeloma (MM) patients has been associated with venous thromboembolism (VTE). Due to the increase in mortality of cancer patients, venous thromboembolism is an important concern for newly diagnosed multiple myeloma (NDMM) patients. The aim of this study was to determine the incidence of thromboembolic events and evaluate associated risk factors among Brazilian NDMM patients using immunomodulators. METHODS: Real-life retrospective cohort study in two Brazilian institutions with newly diagnosed multiple myeloma (NDMM) patients treated with immunomodulators from January 2009 to December 2019. Data was collected from patients' medical records for the period of 1 year, and Cox regression was performed to identify risk factors on the development of VTE. RESULTS: We included 131 patients of which there was a mean age of 61.5 years (SD 11.3), 51.9% female, and predominantly using thalidomide (97.7%) as immunomodulator. We found 9 VTE episodes among our patients, with a 12-month cumulative incidence of 6.97% (95% CI 3.41-12.24). Associated factors after multivariate analysis were recent sepsis, recent traumatic injury, previous VTE, and thromboprophylaxis. CONCLUSION: Our real-life retrospective cohort presented a low incidence of VTE among Brazilian NDMM patients treated with immunomodulators.

Chemotherapy-Induced Peripheral Neuropathy Impacts Quality Of Life And Activities Of Daily Living Of Brazilian Multiple Myeloma Patients.

BACKGROUND: Survival in multiple myeloma (MM) has improved in the past years with the introduction of immunomodulators and proteasome inhibitors. However, chemotherapy-induced peripheral neuropathy (CIPN) is associated with both drug classes affecting Health-Related Quality of Life (HRQoL) and activities of daily living (ADL). OBJECTIVE: We evaluated CIPN in MM patients to identify associated factors and impacts on HRQoL and ADL. METHODS: This is a cross-sectional study with Brazilian patients from public and private health services. Patients were interviewed using validated tools to measure CIPN and HRQoL, along with sociodemographic and clinical questions. Logistic regression was used to assess the association of CIPN with sociodemographic, clinical, and HRQoL variables. RESULTS: In total, 217 patients were eligible for the study. The median age was 67, 50.9% were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide, and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%) had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL. Numbness was the most common symptom (40.6%). CIPN was independently associated with education, hospitalization, chemotherapy, side effects, disease symptoms, and global health status in HRQoL. CONCLUSION: MM patients showed a high frequency of CIPN, which affected ADL and impaired HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide and bortezomib-based regimens should be performed to provide better treatment outcomes and avoid permanent disabilities.

Health-related quality of life and use of medication with anticholinergic activity in patients with multiple myeloma.

PURPOSE: Verify the association between anticholinergic burden and health-related quality of life of patients with multiple myeloma. METHODS: Cross-sectional study with multiple myeloma outpatient from a state capital city in southeastern Brazil. Sociodemographic, clinical, and pharmacotherapeutic variables were collected by interview. Clinical data were complemented by medical records. Drugs with anticholinergic activity were identified with Brazilian Anticholinergic Activity Drug Scale. Health-related quality of life scores were obtained using QLQ-C30 and QLQ-MY20 instruments. Mann-Whitney was used to compare the median of the health-related quality of life scale scores and the independent variables. Multivariate linear regression was performed to verify the association between independent variables and health-related quality of life scores. RESULTS: Two hundred thirteen patients were included, 56.3% had multi-morbidities, and 71.8% used polypharmacy. In all health-related quality of life domains, there were differences between the medians of the polypharmacy variable. A significant difference was identified between the ACh burden and QLQ-C30 and QLQ-MY20 scores. Linear regression identified an association between the use of drugs with anticholinergic activity and the reduction of global status scores (QLQ-C30), functional scale (QLQ-C30), body image (QLQ-MY20), and future perspective (QLQ-MY20). Drugs with anticholinergic activity were associated with increased symptom scores (QLQ-C30 and QLQ-MY20). Polypharmacy was associated with reduction of functioning score and increase of symptom score (QLQ-C30). CONCLUSION: Anticholinergic burden in MM patients is associated with lower scores in quality of life domains: global health and symptoms (QLQ-C30) and functional (QLQ-C30 and QLQ-MY20). The presence of polypharmacy is also associated with lower scores for functional scales and symptom scales (QLQ-C30).

Comparison of three risk assessment models for thromboembolism in multiple myeloma patients receiving immunomodulators: a Brazilian historical cohort.

Venous thromboembolism (VTE) is among the complications of Multiple Myeloma (MM) and may occur in up to 10% of this patient population. However, medications used in MM therapy such as immunomodulators (IMID) may raise these rates. Thus, risk prediction models have been developed to quantify the risk of VTE in MM patients. The aim of this study is to compare the performance of three risk assessment models for VTE in newly diagnosed MM (NDMM) patients using immunomodulatory agents. A historical cohort study during a 10-year period in a Brazilian metropolis with NDMM treated with IMID. Data were collected from patient's medical charts for the period of one year to calculate the scores using IMPEDE VTE, SAVED, and International Myeloma Working Group (IMWG) guidelines. The area under the curve (AUC) of the Receiver Operating Characteristic curve analysis was calculated to assess the discriminative power of three risk assessment models. We included 131 patients (9 in the VTE group versus 122 in the non VTE group). According to IMPEDE, 19.1, 62.6, and 18.3% of patients were considered low, intermediate, and high risk, respectively. SAVED classified 32.1% as high risk and 64.9% had ≥2 risk factors based on IMWG guidelines. The AUC of the IMPEDE VTE score was 0.80 (95% CI 0.66-0.95, p = 0.002), of the SAVED score was 0.69 (95% CI 0.49-0.89, p = 0.057), and of the IMWG risk score was 0.68 (95% CI 0.48-0.88, p = 0.075). IMPEDE VTE was the most accurate in predicting the development of VTE in Brazilian patients on IMID therapy. The SAVED score and the IMWG guidelines did not show discriminative ability in predicting VTE based on the population involved in this study.

Validity and reliability of the QLQ-MY20 module for assessing the health-related quality of life in Brazilians with multiple myeloma.

PURPOSE: Multiple myeloma (MM) is a rare but treatable hematological cancer, which makes the health-related quality of life (HRQoL) an important patient-report outcome measure in clinical studies. The Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to measure HRQoL in people with MM. However, the Brazilian Portuguese version of QLQ-MY20 has not yet been validated for Brazil. This study aimed to evaluate the validity and reliability of the instrument for application in Brazilian patients with MM. METHODS: This is a cross-sectional methodological study with patients seen in health services in Belo Horizonte, Brazil. The variables were collected through face-to-face interviews with the QLQ-MY20 instrument and complemented with data from medical records. Content validity analyses (content validity coefficient [CVC]; correctness ratio), convergent and divergent validity (Spearman's correlation coefficient [CC]), internal consistency, and temporal reproducibility (test-retest; intraclass correlation coefficient [ICC]) were performed. RESULTS: 225 patients were included and 71.1% were older than 60. The analysis of the judging committee showed adequate content validity. We observed mainly a good internal consistency of the items and good discrimination power in the convergent and divergent validity. High ICC values were observed through the test-retest, and there was no difference in the scores between the two moments, which shows good temporal stability of the instrument. CONCLUSION: The study allowed us to conclude that the Brazilian version of the QLQ-MY20 module is valid and reliable, and thus suitable for application in Brazilians living with MM.

Evaluation of water-in-oil-in-water multiple emulsion and microemulsion as potential adjuvants for immunization with rabies antigen.

Water-in-oil-in-water (W/O/W) multiple emulsions and microemulsions have been studied as potential candidates to be formulated as adjuvants. In this work their application as adjuvants for rabies virus immunization was studied. The humoral response, the effective dose 50 and histology for the developed formulations were evaluated in mice and compared with those from traditional adjuvants. The microemulsion and W/O/W multiple emulsion adjuvants developed were able to induce humoral response in mice and the serum showed good in vivo protection. Compared to the other adjuvants evaluated, microemulsion was shown to be the best candidate for rabies immunization as it presented good potency against the virus and did not appear to cause any local reaction.

Inhibition of crotoxin binding to synaptosomes by a receptor-like protein from Crotalus durissus terrificus (the South American rattlesnake).

Crotoxin (Ctx) is a potent neurotoxin of the venom of Crotalus durissus terrificus (the South American rattlesnake). Ctx is a heterodimer composed of CB, a toxic PLA(2) subunit, and CA, a non-toxic and non-enzymatic subunit, that potentiates the neurotoxicity of CB in vivo. The deleterious action of Ctx upon C. d. terrificus snakes themselves is known to be prevented by a PLA(2) inhibitor (CNF) present in their blood serum. CNF acts by replacing CA in Ctx, thus forming a new stable complex CNF-CB. This complex no longer interacts with the target receptor (TR) to deliver CB to cause its lethal effect. Furthermore, CNF-CB seems to be reminiscent of the interaction Ctx-TR at the pre-synaptic site. In the present work, the binding competition between rat brain synaptosomes (TR) and CNF for Ctx was investigated. Radiolabeled Ctx, made of CA and one isoform of CB (CA-(125)ICB(2)), was used as ligand. The competition by unlabeled Ctx was taken as a reference. The potency of CNF as a competitor was evaluated under different incubation conditions with varying time scale addition of reagents (CA-(125)ICB(2), synaptosomes and CA-CB(2) or CNF). CNF was able to inhibit the binding of the toxin to synaptosomes as well as to partially displace the toxin already bound to its membrane target. The mechanisms of competition involved were discussed and a previous schematic model of interactions between Ctx, TR and CNF was updated.