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Annals of Medicine Dec 2023Multiple myeloma (MM) is an incurable malignancy. Venetoclax (VEN) shows a meaningful effect in MM patients who are relapsed or refractory (RR) to previous standard... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple myeloma (MM) is an incurable malignancy. Venetoclax (VEN) shows a meaningful effect in MM patients who are relapsed or refractory (RR) to previous standard therapies.
OBJECTIVE
This study aimed to assess the efficacy and safety of VEN-based treatments in RR MM patients.
MATERIALS AND METHODS
Comprehensive studies were searched in PubMed, Embase, Web of Science and Cochrane library. Efficacy was assessed by overall response rate (ORR), strict complete response rate (sCR), complete response rate (CR), very good partial response rate (VGPR) and partial response rate (PR).
RESULTS
Seven studies containing 482 subjests were included. The pooled ORR, ≥ CR (sCR + CR), VGPR and PR were 68% (51%-85%), 24% (13%-35%), 25% (17%-34%) and 17% (11%-24%) respectively. Multi-drug treatments were superior to VEN ± dexamethasone (Dex) treatments in ORR (82% vs 42%, = .003) and ≥ CR (36% vs 7%, < 0.00001). Subgroup analysis indicated patients achieve higher ORR who harboring t(11;14) translocation or containing high BCL-2 expression.
CONCLUSIONS
VEN-containing regimens could be suggested as effective and safe treatments to RR MM patients with t(11;14) or high BCL-2 levels.
Topics: Humans; Multiple Myeloma; Prospective Studies; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 36911885
DOI: 10.1080/07853890.2023.2186480 -
Synergistically Anti-Multiple Myeloma Effects: Flavonoid, Non-Flavonoid Polyphenols, and Bortezomib.Biomolecules Nov 2022Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. Bortezomib(BTZ), a first-generation protease inhibitor, has... (Review)
Review
Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. Bortezomib(BTZ), a first-generation protease inhibitor, has increased overall survival, progression-free survival, and remission rates in patients with MM since its clinical approval in 2003. However, the use of BTZ is challenged by the malignant features of MM and drug resistance. Polyphenols, classified into flavonoid and non-flavonoid polyphenols, have potential health-promoting activities, including anti-cancer. Previous preclinical studies have demonstrated the anti-MM potential of some dietary polyphenols. Therefore, these dietary polyphenols have the potential to be alternative therapies in anti-MM treatment regimens. This systematic review examines the synergistic effects of flavonoids and non-flavonoid polyphenols on the anti-MM impacts of BTZ. Preclinical studies on flavonoids and non-flavonoid polyphenols-BTZ synergism in MM were collected from PubMed, Web of Science, and Embase published between 2008 and 2020. 19 valid preclinical studies (Published from 2008 to 2020) were included in this systematic review. These studies demonstrated that eight flavonoids (icariin, icariside II, (-)-epigallocatechin-3-gallate, scutellarein, wogonin, morin, formononetin, daidzin), one plant extract rich in flavonoids (Punica granatum juice) and four non-flavonoid polyphenols (silibinin, resveratrol, curcumin, caffeic acid) synergistically enhanced the anti-MM effect of BTZ. These synergistic effects are mediated through the regulation of cellular signaling pathways associated with proliferation, apoptosis, and drug resistance. Given the above, flavonoids and non-flavonoid polyphenols can benefit MM patients by overcoming the challenges faced in BTZ treatment. Despite the positive nature of this preclinical evidence, some additional investigations are still needed before proceeding with clinical studies. For this purpose, we conclude by providing some suggestions for future research directions.
Topics: Humans; Bortezomib; Multiple Myeloma; Polyphenols; Apoptosis; Molecular Targeted Therapy; Cell Line, Tumor; Antineoplastic Agents; Drug Resistance, Neoplasm
PubMed: 36358997
DOI: 10.3390/biom12111647 -
Otology & Neurotology : Official... Apr 2024To examine the otologic and neurotologic symptoms, physical examination findings, and imaging features secondary to hematologic malignancies. (Review)
Review
OBJECTIVE
To examine the otologic and neurotologic symptoms, physical examination findings, and imaging features secondary to hematologic malignancies.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases, including PubMed, Scopus, and CINAHL, were searched for articles including patients with otologic manifestations of leukemia, lymphoma and multiple myeloma. Data collected included patient and study demographics, specific hematologic malignancy, timing and classification of otologic symptoms, physical examination findings, imaging features and methods of diagnosis. Pooled descriptive analysis was performed.
RESULTS
Two hundred seventy-two articles, of which 255 (93.8%) were case reports and 17 (6.2%) were case series, reporting on 553 patients were identified. Otologic manifestations were reported on 307 patients with leukemia, 204 patients with lymphoma and 42 patients with multiple myeloma. Hearing loss and unilateral facial palsy were the most common presenting symptoms for 111 reported subjects with leukemia (n = 46, 41.4%; n = 43, 38.7%) and 90 with lymphoma (n = 38, 42.2%; n = 39, 43.3%). Hearing loss and otalgia were the most common presenting symptoms for 21 subjects with multiple myeloma (n = 10, 47.6%; n = 6, 28.6%). Hearing loss and unilateral facial palsy were the most common otologic symptoms indicative of relapse in subjects with leukemia (n = 14, 43.8%) and lymphoma (n = 5, 50%).
CONCLUSION
Hearing loss, facial palsy, and otalgia might be the first indication of a new diagnosis or relapse of leukemia, lymphoma, or multiple myeloma. Clinicians should have a heightened level of suspicion of malignant etiologies of otologic symptoms in patients with current or medical histories of these malignancies.
Topics: Humans; Earache; Facial Paralysis; Multiple Myeloma; Hearing Loss; Hematologic Neoplasms; Deafness; Leukemia; Bell Palsy; Lymphoma; Recurrence
PubMed: 38437804
DOI: 10.1097/MAO.0000000000004141 -
Clinical Rheumatology Feb 2023Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones... (Review)
Review
Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.
Topics: Humans; Rituximab; Cryoglobulinemia; Consensus; Hepatitis C; Hepacivirus; Vasculitis
PubMed: 36169798
DOI: 10.1007/s10067-022-06391-w -
International Journal of Molecular... May 2024Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell)... (Meta-Analysis)
Meta-Analysis Review
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy's efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.
Topics: Multiple Myeloma; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Treatment Outcome; Quality of Life; Neoplasm Recurrence, Local; Cytokine Release Syndrome
PubMed: 38732213
DOI: 10.3390/ijms25094996 -
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 -
Clinical Chemistry and Laboratory... Nov 2023Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits)....
Recommendations for the study of monoclonal gammopathies in the clinical laboratory. A consensus of the Spanish Society of Laboratory Medicine and the Spanish Society of Hematology and Hemotherapy. Part I: Update on laboratory tests for the study of monoclonal gammopathies.
Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits). This abnormal immunoglobulin component is called monoclonal protein (M-protein), and is considered a biomarker of proliferative activity. The identification, characterization and measurement of M-protein is essential for the management of MG. We conducted a systematic review of the different tests and measurement methods used in the clinical laboratory for the study of M-protein in serum and urine, the biochemistry and hematology tests necessary for clinical evaluation, and studies in bone marrow, peripheral blood and other tissues. This review included literature published between 2009 and 2022. The paper discusses the main methodological characteristics and limitations, as well as the purpose and clinical value of the different tests used in the diagnosis, prognosis, monitoring and assessment of treatment response in MG. Included are methods for the study of M-protein, namely electrophoresis, measurement of immunoglobulin levels, serum free light chains, immunoglobulin heavy chain/light chain pairs, and mass spectrometry, and for the bone marrow examination, morphological analysis, cytogenetics, molecular techniques, and multiparameter flow cytometry.
Topics: Humans; Laboratories, Clinical; Consensus; Paraproteinemias; Immunoglobulin Light Chains; Hematology; Multiple Myeloma
PubMed: 37477188
DOI: 10.1515/cclm-2023-0326 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2022Tumor necrosis factor alpha (TNF-α) is a cytokine with a key role in proinflammation and multiple diseases, including cancer. The gene encoding TNF-α is located within... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Tumor necrosis factor alpha (TNF-α) is a cytokine with a key role in proinflammation and multiple diseases, including cancer. The gene encoding TNF-α is located within a highly polymorphic region on chromosome 6p21.3; two polymorphisms -308G/A (rs1800629) and -238G/A (rs361525) have been associated with occurrence of human diseases. There is a debate in recent meta-analyses that reached discrepant conclusions regarding the potential role of TNF-α polymorphisms in multiple myeloma (MM) risk. The aim of this systematic review and meta-analysis is to investigate the association between the aforementioned two polymorphisms with the risk and survival of MM.
MATERIALS AND METHODS
Eligible articles were identified through an extensive search in PubMed database (end of search: June 18, 2020). The pooled effect estimates were calculated following the random-effects models by Der Simonian and Laird. Separate analyses were conducted by ethnicity. Between-study heterogeneity was quantified, and the deviation of genotype frequencies in controls from the Hardy-Weinberg equilibrium was evaluated.
RESULTS
Eighteen studies (2934 cases, 4291 controls) have been included in the quantitative synthesis examining risk and 5 studies for survival (557 cases). No association was found between -308G/A and -238G/A TNF-α polymorphisms and MM susceptibility in all genetic models for both Caucasian and East Asian populations. There was no association between -308G/A and -238G/A TNF-α polymorphisms and survival (overall or progression-free) of MM.
CONCLUSION
This systematic review and meta-analysis did not reveal a significant effect of -308G/A and -238G/A TNF-α polymorphisms upon risk or survival of MM.
Topics: Asian People; Case-Control Studies; Genetic Predisposition to Disease; Humans; Multiple Myeloma; Polymorphism, Single Nucleotide; Tumor Necrosis Factor-alpha
PubMed: 34642126
DOI: 10.1016/j.clml.2021.08.010 -
Critical Reviews in Oncology/hematology Mar 2021This study aims to evaluate the efficacy and safety of Daratumumab-based induction therapy (DBI) in newly diagnosed multiple myeloma (MM). We identified four eligible... (Meta-Analysis)
Meta-Analysis Review
This study aims to evaluate the efficacy and safety of Daratumumab-based induction therapy (DBI) in newly diagnosed multiple myeloma (MM). We identified four eligible RCTs including 2735 patients. The primary outcomes of RCTs involving transplant eligible (TEMM) and non-transplant eligible MM (NTEMM) were stringent complete response (sCR) and progression-free survival (PFS) respectively. Meta-analysis was performed using random-effects models. DBI improved sCR rates for standard risk (SR) (OR 1.86, 95 % CI 1.41-2.46) but not HiR (high risk) (OR 0.78, 95 % CI 0.41-1.48) (interaction P = 0.01) TEMM. In NTEMM, DBI improved PFS in SR (HR 0.44, 95 % CI 0.35-0.55) but not HiR patients. (HR 0.81, 95 % CI 0.52-1.27) (interaction P = 0.02). In conclusion, while DBI is efficacious in SR patients, there is insufficient data to support a benefit in HiR-MM.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Humans; Induction Chemotherapy; Multiple Myeloma
PubMed: 33387628
DOI: 10.1016/j.critrevonc.2020.103211 -
BMC Cancer May 2023Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival (PFS) and overall survival (OS) benefit with HDT/ASCT.
METHODS
We conducted a systematic review and meta-analysis that included both randomized controlled trials (RCTs) and observational studies evaluating the benefit of upfront HDT/ASCT published during 2012 to 2023. Further sensitivity analysis and meta-regression were also performed.
RESULTS
Among the 22 enrolled studies, 7 RCTs and 9 observational studies had a low or moderate risk of bias, while the remaining 6 observational studies had a serious risk of bias. HDT/ASCT revealed advantages in complete response (CR) with an odds ratio (OR) of 1.24 and 95% confidence interval (CI) 1.02 ~ 1.51, PFS with a hazard ratio (HR) of 0.53 (95% CI 0.46 ~ 0.62), and OS with an HR of 0.58 (95% CI 0.50 ~ 0.69). Sensitivity analysis excluding the studies with serious risk of bias and trim-and-fill imputation fundamentally confirmed these findings. Older age, increased percentage of patients with International Staging System (ISS) stage III or high-risk genetic features, decreased proteasome inhibitor (PI) or combined PI/ immunomodulatory drugs (IMiD) utilization, and decreased follow-up duration or percentage of males were significantly related to a greater survival advantage with HDT/ASCT.
CONCLUSIONS
Upfront ASCT remains a beneficial treatment for newly diagnosed MM patients in the period of novel agents. Its advantage is especially acute in high-risk MM populations, such as elderly individuals, males, those with ISS stage III or high-risk genetic features, but is attenuated with PI or combined PI/IMiD utilization, contributing to divergent survival outcomes.
Topics: Male; Humans; Aged; Multiple Myeloma; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Transplantation, Autologous; Disease-Free Survival; Stem Cell Transplantation
PubMed: 37193978
DOI: 10.1186/s12885-023-10907-1