-
Journal of Oncology Pharmacy Practice :... Apr 2024The plasma cell malignancy, multiple myeloma (MM), remains incurable despite advanced treatment protocols. Overexpression of Bcl-2 (an anti-apoptotic protein), in MM...
BACKGROUND
The plasma cell malignancy, multiple myeloma (MM), remains incurable despite advanced treatment protocols. Overexpression of Bcl-2 (an anti-apoptotic protein), in MM harboring the translocation (11;14), contributes to resistance to prior therapy. Venetoclax, a selective oral inhibitor of BCL-2 is a novel agent that shows promise as a therapeutic agent.
AIMS
The objective of this systematic review is to address how the use of venetoclax, alone or as a combination regimen, contributed to the treatment of patients with t(11:14) positive relapsed/refractory multiple myeloma (RRMM).
DATA SOURCES
This systematic review was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was done on 5th June 2022. A literature search was conducted on PubMed and Scopus, 145 articles were screened and 10 studies were included. Risk of bias assessment was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria.
DATA SUMMARY
Across the studies reviewed, a total of 311 patients were identified with t(11;14) positive RRMM. The overall response rate achieved ranged between 33% and 95.5%. Furthermore, the use of venetoclax has exhibited a favorable adverse effect profile. Side effects included hematological side effects, nausea, vomiting, and diarrhea.
CONCLUSION
Venetoclax demonstrates promising results. When given with drugs like dexamethasone, daratumumab and carfilzomib, a synergistic effect is seen in treating translocation (11:14) positive relapsed/refractory MM. The use of venetoclax in clinical practice can potentially improve outcomes and quality of life in RRMM patients, and future research should continue to explore this promising treatment option.
Topics: Humans; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Drug Resistance, Neoplasm; Multiple Myeloma; Neoplasm Recurrence, Local; Sulfonamides; Translocation, Genetic
PubMed: 38113108
DOI: 10.1177/10781552231218999 -
Cancer Epidemiology Dec 2023This systematic review examines the relationship with multiple myeloma (MM) risk for sunlight and vitamin D related exposures, including vitamin D supplementation,... (Meta-Analysis)
Meta-Analysis Review
This systematic review examines the relationship with multiple myeloma (MM) risk for sunlight and vitamin D related exposures, including vitamin D supplementation, circulating 25-hydroxyvitamin D concentration, personal ultraviolet B radiation exposure, ambient solar irradiance and vitamin D receptor (VDR) gene polymorphisms We conducted a search for terms related to multiple myeloma, vitamin D, vitamin D receptor, ultraviolet radiation, sunlight, and single nucleotide polymorphism (SNP) using Ovid MEDLINE, Ovid EMBASE, Web of Science and Cochrane CENTRAL. Studies were assessed for risk of bias and quality using the RoB 2.0, ROBINS-E or Q-Genie tools. We identified 13 eligible studies: one randomised controlled trial, two cohort studies, and ten case-control studies, including one nested case-control study and one meta-analysis of genome-wide association studies. We conducted a qualitative synthesis; quantitative synthesis was not appropriate due to study heterogeneity and the small number of studies identified. There was insufficient evidence to support an effect of any sunlight or vitamin D related exposure on MM risk. No polymorphisms in VDR were found to be strongly related to risk for people of European ancestry. Of the identified studies, many had high risk of bias or were of lower quality. Few studies have investigated the association between sunlight and vitamin D related exposures and multiple myeloma risk. The scarcity of high-quality studies makes it difficult to evaluate potential effects of these exposures on MM risk. Further research is necessary to investigate the influence of vitamin D related exposures on risk of multiple myeloma..
Topics: Humans; Case-Control Studies; Genome-Wide Association Study; Multiple Myeloma; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Sunlight; Ultraviolet Rays; Vitamin D
PubMed: 37976630
DOI: 10.1016/j.canep.2023.102488 -
Diagnostics (Basel, Switzerland) Nov 2023Artificial intelligence (AI) has attracted increasing attention as a tool for the detection and management of several medical conditions. Multiple myeloma (MM), a... (Review)
Review
Artificial intelligence (AI) has attracted increasing attention as a tool for the detection and management of several medical conditions. Multiple myeloma (MM), a malignancy characterized by uncontrolled proliferation of plasma cells, is one of the most common hematologic malignancies, which relies on imaging for diagnosis and management. We aimed to review the current literature and trends in AI research of MM imaging. This study was performed according to the PRISMA guidelines. Three main concepts were used in the search algorithm, including "artificial intelligence" in "radiologic examinations" of patients with "multiple myeloma". The algorithm was used to search the PubMed, Embase, and Web of Science databases. Articles were screened based on the inclusion and exclusion criteria. In the end, we used the checklist for Artificial Intelligence in Medical Imaging (CLAIM) criteria to evaluate the manuscripts. We provided the percentage of studies that were compliant with each criterion as a measure of the quality of AI research on MM. The initial search yielded 977 results. After reviewing them, 14 final studies were selected. The studies used a wide array of imaging modalities. Radiomics analysis and segmentation tasks were the most popular studies (10/14 studies). The common purposes of radiomics studies included the differentiation of MM bone lesions from other lesions and the prediction of relapse. The goal of the segmentation studies was to develop algorithms for the automatic segmentation of important structures in MM. Dice score was the most common assessment tool in segmentation studies, which ranged from 0.80 to 0.97. These studies show that imaging is a valuable data source for medical AI models and plays an even greater role in the management of MM.
PubMed: 37958267
DOI: 10.3390/diagnostics13213372 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2024Multiple myeloma (MM) accounts for 10% of hematologic cancers in the U.S.; however, incidence and mortality occur disproportionately between racial groups in real-world...
Multiple myeloma (MM) accounts for 10% of hematologic cancers in the U.S.; however, incidence and mortality occur disproportionately between racial groups in real-world settings. Our study's objective was to systematically characterize the disparities in overall survival (OS) among Black and White patients with MM in the US using real-world evidence studies. A systematic literature review was undertaken by searching Embase and MEDLINE for observational studies conducted in the US, published between January 1, 2015 and October 25, 2021, and reporting OS for Black and White patients with MM. Records were reviewed by 2 independent researchers. OS data were extracted as hazard ratios (HR), median survival, or %, with methods of adjustment, as reported. Evidence quality was assessed by data source, population, and variables for which HRs for risk of death were adjusted. We included 33 US studies comprising 410,086 patients (21.5% Black; 78.5% White) with MM. Receipt of treatment varied; however, most studies reported that patients either underwent stem cell transplant and/or received systemic therapy. HRs from 9 studies were considered "high quality" by comparing nationally representative, generalizable cohorts and adjusting for key prognostic, treatment, and/or socioeconomic factors. After adjustment, these data suggested that Black patients exhibit similar or superior survival outcomes compared with their White counterparts. When data are adjusted for important confounders, Black patients exhibit better or equal survival to White patients, indicating that similarities in patient populations and equal access to treatment can bridge the disparity in patient outcomes between races.
Topics: Humans; Healthcare Disparities; Multiple Myeloma; Proportional Hazards Models; Racial Groups; Black or African American; White; Survival Rate
PubMed: 37923653
DOI: 10.1016/j.clml.2023.09.009 -
Hematology (Amsterdam, Netherlands) Dec 2023High-risk multiple myeloma (HRMM) is associated with poor survival, despite many advances in antimyeloma strategies. Autologous followed by allogeneic stem cell... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
High-risk multiple myeloma (HRMM) is associated with poor survival, despite many advances in antimyeloma strategies. Autologous followed by allogeneic stem cell transplantation (auto-allo-SCT) has yielded controversial results compared to tandem autologous stem cell transplantation (auto-SCT) in patients with HRMM. We conducted this meta-analysis to compare the efficacy and safety of auto-allo-SCT and tandem-auto-SCT in patients with HRMM.
METHODS
Embase, Cochrane Library, and PubMed databases were searched until March 2023. Prospective or retrospective studies comparing the effects of auto-allo-SCT and tandem-auto-SCT were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) for time-to-event outcomes, and odds ratios (ORs) and 95%CIs for dichotomous outcomes were pooled using random-effects models.
RESULTS
Three studies involving 491 patients were included. Despite auto-allo-SCT seemed to be associated with improvements in progression-free survival (PFS) (HR [95%CI], 0.71 [0.51-1.00]) and complete response (CR) (OR [95%CI], 3.16 [1.67-5.99]), and reduced relapse/progression rates (47% vs. 55%) in comparison with tandem-auto-SCT, no marked improvement in overall survival (OS). In comparison to tandem-auto-SCT, patients assigned to auto-allo-SCT exhibited a higher risk of transplant-related mortality (TRM) (11.9% vs. 4.1%) and non-relapse mortality (NRM) (12.3% vs. 3.1%).
CONCLUSION
Auto-allo-SCT seemed to be associated with improvements in PFS and CR when compared to tandem-auto-SCT in patients with HRMM, but it did not lead to a significant improvement in OS. Furthermore, patients in the auto-allo-SCT group were at a higher risk of developing TRM and NRM. Auto-allo-SCT transplantation should not be routinely incorporated into HRMM therapy but rather should be considered investigational.
Topics: Humans; Transplantation, Autologous; Multiple Myeloma; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Retrospective Studies; Prospective Studies; Neoplasm Recurrence, Local
PubMed: 37850613
DOI: 10.1080/16078454.2023.2269509 -
Atherosclerosis Plus Dec 2023To systematically investigate all relevant evidence on the association between high-density lipoprotein cholesterol (HDL-C) and multiple myeloma (MM).
BACKGROUND AND AIMS
To systematically investigate all relevant evidence on the association between high-density lipoprotein cholesterol (HDL-C) and multiple myeloma (MM).
METHODS
We searched PubMed and Cochrane library databases (up to 20 September 2022) for studies with evidence on HDL-C in patients with MM. A qualitative synthesis of published prospective and retrospective studies for the role of HDL-C and other lipid profile parameters in MM was performed. Additionally, a meta-analysis on HDL-C mean differences (MD) between MM cases and controls was performed.
RESULTS
Fourteen studies (3 prospective, 11 retrospective) including 895 MM patients were eligible for this systematic review. Ten studies compared HDL-C levels in MM patients with healthy controls. In these 10 studies (n = 17,213), pooled analyses showed that MM patients had significantly lower HDL-C levels compared to healthy controls (MD: -13.07 mg/dl, 95% CI: -17.83, -8.32, p < 0.00001). Regarding secondary endpoints, total cholesterol (TC) (MD: -22.19 mg/dl, 95% CI: -39.08, -5.30) and apolipoprotein A-I (apoA-I) (-40.20 mg/dl, 95% CI: -55.00, -25.39) demonstrated significant decreases, while differences in low-density lipoprotein cholesterol (LDL-C) (MD: -11.33 mg/dl, 95% CI: -36.95, 14.30) and triglycerides (MD: 9.93 mg/dl, 95% CI: -3.40, 23.26) were not shown to be significant.
CONCLUSIONS
HDL-C, as well as TC and apoA-I, levels are significantly decreased in MM. Hence, lipid profile parameters should be taken into account when assessing such patients.
PubMed: 37780686
DOI: 10.1016/j.athplu.2023.09.003 -
Critical Reviews in Oncology/hematology Dec 2023A registered (PROSPERO - CRD42022346462) systematic review and meta-analysis was conducted of all-grade infections amongst adult patients receiving CAR-T therapy for... (Meta-Analysis)
Meta-Analysis Review
A registered (PROSPERO - CRD42022346462) systematic review and meta-analysis was conducted of all-grade infections amongst adult patients receiving CAR-T therapy for haematological malignancy. Meta-analysis of pooled incidence, using random effects model, was conducted. Cochran's Q test examined heterogeneity. 2678 patients across 33 studies were included in the primary outcome. Forty-percent of patients (95% CI: 0.33 - 0.48) experienced an infection of any grade. Twenty-five percent of infection events (95% CI: 0.16 - 0.34) were severe. Late infections were as common as early infections (IRR = 0.86, 95% CI: 0.38 - 1.98). All-grade infections, bacterial and viral infections were highest in myeloma patients at 57%, 37% and 28% respectively. Patients with NHL more commonly experienced late infections. Pooled rate of invasive candidiasis/yeast infections was 2% in studies utilizing anti-yeast prophylaxis. This review identified a high rate of all-grade infections, moderate rate of severe infections, and myeloma as a high-risk haematological group.
Topics: Adult; Humans; Multiple Myeloma; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Hematologic Neoplasms; Hematology
PubMed: 37739146
DOI: 10.1016/j.critrevonc.2023.104134 -
Journal of Geriatric Oncology Mar 2024Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy is transforming the care of patients with relapsed/refractory multiple myeloma... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy is transforming the care of patients with relapsed/refractory multiple myeloma (MM). Unfortunately, despite being a disease of older adults these patients remain under-represented in most pivotal clinical trials. We performed a systematic review and proportion meta-analysis of prospective clinical trials and observational studies of anti-BCMA CAR-T therapy in patients with MM with the aim to determine the efficacy and safety of this therapy in older adults (≥65 years).
MATERIALS AND METHODS
We searched the Pubmed, Scopus, Web of Science (WOS), Ovid, Embase, CENTRAL, and CINAHL databases through September 9, 2022 and abstracts from the American Society of Hematology (ASH) Annual Meeting 2022. Primary outcome measures included overall response rate (ORR), rates of cytokine release syndrome (CRS), and immune cell-effector-associated neurotoxicity syndrome (ICANS). study was registered with PROSPERO (study number: CRD42022334287).
RESULTS
After screening 2218 references, 14 studies were included for data extraction, with a total of 558 patients, 26.2% (n = 146) of whom were older adults. The pooled ORR amongst this population was 93%, which was comparable to the ORR of 86% amongst younger patients. In older adults, the rates of CRS (any grade) and grade ≥ 3 were 95% and 21%, respectively. For younger patients, the pooled rate of CRS (any grade) and grade ≥ 3 CRS was 91% and 20%, respectively. The rate of ICANS (any grade) in older adults was 15%, which was higher than that observed in those <65 years.
CONCLUSION
Older adults experience comparable outcomes to younger patients with anti-BCMA CAR-T therapy, albeit with numerically higher rates of neurotoxicity.
Topics: Humans; Aged; Multiple Myeloma; Receptors, Chimeric Antigen; Prospective Studies; Immunotherapy, Adoptive; Cell- and Tissue-Based Therapy; Observational Studies as Topic
PubMed: 37723045
DOI: 10.1016/j.jgo.2023.101628 -
Head & Neck Nov 2023The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However,... (Meta-Analysis)
Meta-Analysis Review
The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However, these data are from small cohorts and available tests for detection of ctHPVDNA are not fully validated. The aim is to evaluate sensitivity, specificity, and accuracy of ctHPVDNA by ddPCR to define its efficacy in the clinical setting for the diagnosis of HPV + OPSCC. A comprehensive search of three different databases: MEDLINE, Embase, and Cochrane Library databases. A total of 998 patients were evaluated from the 13 studies. OPSSC p16+ were 729, while controls p16- were 269. The meta-analytic study estimated the diagnostic performance of ctHPVDNA as follows: pooled sensitivity and specificity of 0.90 (95% CI: 0.82-0.94) and 0.94 (95% CI: 0.85-0.98), respectively; positive and negative likelihood ratios of 12.6 (95% CI: 4.9-32.1) and 0.05 (95% CI: 0.02-0.13), respectively. ddPCR for ctHPVDNA has good accuracy, sensitivity, and specificity for diagnosis of HPV + OPSCC. ctHPVDNA kinetic represents a great reliable opportunity to improve diagnostic and therapeutic management of cancer patients and could open new perspectives for understanding tumor biology.
Topics: Humans; Papillomavirus Infections; Circulating Tumor DNA; Papillomaviridae; Oropharyngeal Neoplasms; Human Papillomavirus Viruses; DNA, Viral; Head and Neck Neoplasms
PubMed: 37715656
DOI: 10.1002/hed.27515 -
World Neurosurgery Dec 2023Plasma cell granuloma (PCG) is a rare clinical entity seen in the neurosurgical literature. It has often been referred to as inflammatory myofibroblastic tumor or... (Review)
Review
BACKGROUND
Plasma cell granuloma (PCG) is a rare clinical entity seen in the neurosurgical literature. It has often been referred to as inflammatory myofibroblastic tumor or inflammatory pseudotumor. No well-defined management guidelines exist in the literature.
METHODS
Using PRISMA guidelines, we systematically reviewed the literature in PubMed and Google Scholar using MeSH terms: intracranial plasma cell granuloma, myofibroblastic tumor, intracranial pseudotumor, spinal plasma cell granuloma. We analyzed the clinical presentation, treatment strategies, clinical outcomes, and follow-up across different studies.
RESULTS
Eighty-three studies were included presenting 108 cases. Primary extracranial disease was seen in 4 patients and primary central nervous system (CNS) disease in 104. In the combined cohort, multicompartmental disease was seen in 22 (20.8%) patients. Headache (n=40, 42.59%) was the most common clinical symptom. Surgical excision (n=86, 79.6%) was the most common primary treatment used. Radiation therapy, steroids, and chemotherapy (methotrexate/6-mercaptopurine/rituximab) were also used. Disease recurrence was noted in 25 (33.3%) patients and residual disease in 33 (30.5%). Mortality was seen in 4 (3.7%) patients. In the cranial PCG subgroup (n=87), 81 (93.1%) patients had solitary lesions, and 6 (6.8%) had multiple lesions. Recurrence after primary surgery was noted in 27.58% (n=24). In the spinal PCG subgroup (n=17), the thoracic spine was the most common location (n=9, 52.9%) and recurrence was seen in 5.84% (n=1).
CONCLUSIONS
Combination of multiple treatment modalities is needed when approaching this complex disease. Spinal PCGs respond favorably to gross total excision, with a low recurrence rate. Cranial PCGs warrant intense follow-up with secondary chemotherapy/radiation/steroids in recurrent cases.
Topics: Humans; Granuloma, Plasma Cell; Neoplasm Recurrence, Local; Central Nervous System; Rituximab; Steroids
PubMed: 37708970
DOI: 10.1016/j.wneu.2023.09.026