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Frontiers in Immunology 2024Bispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Bispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients.
METHODS
PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs.
RESULTS
Fourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% . 54%, < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% . 18%, < 0.01; grade ≥ 3: 43% . 15%, < 0.01) and lymphopenia (any grade: 37% . 8%, < 0.01; grade ≥ 3: 31% . 8%, = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% . 66%, = 0.84; grade ≥ 3: 1% . 1%, = 0.36) and infections (any grade: 47% . 49%, = 0.86; grade ≥ 3: 24% . 20%, = 0.06) between the two groups. However, non-BCMA-targeted BsAbs therapy was associated with a higher risk of immune effector cell-associated neurotoxicity syndrome (ICANS, any grade: 11% . 2%, < 0.01) and lower risks of fatigue (any grade: 14% . 30%, < 0.01) and pyrexia (any grade: 14% . 29%, < 0.01).
CONCLUSION
This analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.
Topics: Humans; Multiple Myeloma; Antibodies, Bispecific; B-Cell Maturation Antigen; Prospective Studies; Neurotoxicity Syndromes; Neutropenia
PubMed: 38482019
DOI: 10.3389/fimmu.2024.1348955 -
Annals of Medicine Dec 2024The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with... (Meta-Analysis)
Meta-Analysis
AIM
The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF + plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile.
METHODS
We performed a database search using the terms 'granulocyte colony stimulating factor', 'G-CSF', 'AMD3100', and 'plerixafor', published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760).
RESULTS
Twenty-three studies were included in this systematic review and meta-analysis. G-CSF + plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34-6.55). It was further discovered that G-CSF + plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74-27.85) and single-arm (MD, 20.67; 95%, 14.34-27.00) trials. Furthermore, G-CSF + plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87-1.80).
CONCLUSIONS
This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB.
Topics: Humans; Hematopoietic Stem Cell Mobilization; Multiple Myeloma; Granulocyte Colony-Stimulating Factor; Heterocyclic Compounds; Lymphoma; Lymphoma, Non-Hodgkin; Hematopoietic Stem Cells; Transplantation, Autologous; Benzylamines; Hematopoietic Stem Cell Transplantation
PubMed: 38470973
DOI: 10.1080/07853890.2024.2329140 -
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 -
Expert Review of Hematology 2024To evaluate the efficacy and safety of pomalidomide in combination treatment of relapsed/refractory multiple myeloma (RRMM). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To evaluate the efficacy and safety of pomalidomide in combination treatment of relapsed/refractory multiple myeloma (RRMM).
METHODS
Published clinical trials were searched in the Cochrane Library, PubMed, EMBASE to February 2023. The literature was screened and evaluated according to the inclusion criteria, and the data were analyzed by a random effect model. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and full grade or ≥ 3 adverse events (AEs) were the outcomes.
RESULTS
This study included 31 clinical trials, which included 4776 patients. The pooled ORR of the doublet regimens was 33.3% (95%CI: 27-39%) and the triplet regimens was 66% (95%CI: 58-74%). Among the 25 included studies, the median PFS was 8.29 months (95%CI: 7.27-9.31), and nine studies reported median OS of 19.43 months (95%CI: 14.56-24.30). In terms of safety, the most common hematologic AEs of grade ≥ 3 were neutropenia (41%) and anemia (20%); Non-hematologic AEs were pneumonia (14%) and infection/febrile neutropenia (14%).
CONCLUSIONS
Pomalidomide combined treatment regimens have shown good clinical efficacy, especially in pomalidomide + dexamethasone combined with other drugs. In terms of safety, it's important to pay attention to the likelihood of hematological adverse events when used clinically.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO: CRD42023420644.
Topics: Multiple Myeloma; Humans; Thalidomide; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Recurrence; Treatment Outcome
PubMed: 38421372
DOI: 10.1080/17474086.2024.2326219 -
International Journal of Cardiology May 2024This systematic review aimed to assess the tolerability of patients with cardiac amyloidosis (CA) to beta-blockers (BBs) and evaluate its association with adverse... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review aimed to assess the tolerability of patients with cardiac amyloidosis (CA) to beta-blockers (BBs) and evaluate its association with adverse outcomes.
METHODS
We performed a comprehensive search from January 1, 2000 to October 20, 2023. Studies examining BB use and tolerance or the relationship between BB use and outcomes in patients with CA were included. Pooled adjusted hazard ratios (aHRs) for all-cause mortality were calculated using random- and fixed-effects models.
RESULTS
Eight observational studies involving 4002 patients with CA (87.5% with transthyretin CA [ATTR-CA] and 12.5% with immunoglobulin light chain CA [AL-CA]) were assessed. BBs were used by 52.5% of the patients. However, 26.3% of the patients discontinued BBs because of hypotension, bradycardia, or fatigue. Regarding the association between BB use and all-cause death, four studies were identified that included 2874 patients with ATTR-CA and 16 patients with AL-CA. The meta-analysis revealed no apparent relationship between BB use and all-cause mortality (pooled aHR = 0.78, 95% confidence interval (CI) = 0.40-1.51). Two studies on patients with ATTR-CA found no impact of BB use on all-cause mortality in the subgroup with left ventricular ejection fraction (LVEF) > 40%, but conflicting results exist for those with LVEF ≤40% (pooled aHR = 0.78, 95% CI = 0.40-1.54).
CONCLUSION
The limited number of observational studies that predominantly enrolled patients with ATTR-CA showed that BBs were used in almost half of the patients with CA, with varying tolerability. However, no significant association was observed between BB use and all-cause mortality.
Topics: Humans; Amyloid Neuropathies, Familial; Stroke Volume; Ventricular Function, Left; Immunoglobulin Light-chain Amyloidosis; Prealbumin; Cardiomyopathies
PubMed: 38278490
DOI: 10.1016/j.ijcard.2024.131813 -
Blood Cancer Journal Jan 2024Extra copies of chromosome 1q21 (+1q: gain = 3 copies, amp >= 4 copies) are associated with worse outcomes in multiple myeloma (MM). This systematic review assesses...
Extra copies of chromosome 1q21 (+1q: gain = 3 copies, amp >= 4 copies) are associated with worse outcomes in multiple myeloma (MM). This systematic review assesses the current reporting trends of +1q, the efficacy of existing regimens on +1q, and its prognostic implications in MM randomized controlled trials (RCTs). Pubmed, Embase and Cochrane Registry of RCTs were searched from January 2012 to December 2022. Only MM RCTs were included. A total of 124 RCTs were included, of which 29 (23%) studies reported on +1q. Among them, 10% defined thresholds for +1q, 14% reported survival data separately for gain and amp, and 79% considered +1q a high-risk cytogenetic abnormality. Amongst RCTs that met the primary endpoint showing improvement in progression free survival (PFS), lenalidomide maintenance (Myeloma XI), selinexor (BOSTON), and isatuximab (IKEMA and ICARIA) were shown to improve PFS for patients with evidence of +1q. Some additional RCT's such as Myeloma XI+ (carfilzomib), ELOQUENT-3 (elotuzumab), and HOVON-65/GMMG-HD4 (bortezomib) met their endpoint showing improvement in PFS and also showed improvement in PFS in the +1q cohort, although the confidence interval crossed 1. All six studies that reported HR for +1q patients vs. without (across both arms) showed worse OS and PFS for +1q. There is considerable heterogeneity in the reporting of +1q. All interventions that have shown to be successful in RCTs and have clearly reported on the +1q subgroup have shown concordant direction of results and benefit of the applied intervention. A more standardized approach to reporting this abnormality is needed.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Chromosome Aberrations; Chromosomes, Human, Pair 1; Lenalidomide; Multiple Myeloma; Prognosis; Randomized Controlled Trials as Topic
PubMed: 38272897
DOI: 10.1038/s41408-024-00985-0 -
BMC Nephrology Jan 2024It is crucial to identify patients with monoclonal gammopathy of renal significance (MGRS) from those without MGRS but with monoclonal gammopathy and concomitant kidney... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is crucial to identify patients with monoclonal gammopathy of renal significance (MGRS) from those without MGRS but with monoclonal gammopathy and concomitant kidney diseases. However, there have been few studies with large sample sizes, and their findings were inconsistent. This study aimed to conduct a meta-analysis of MGRS to describe the general characteristics of MGRS and its predictive factors.
METHODS
Cohort or case-control studies published through December 2022 and related to clinicopathological features of MGRS were retrieved from the PubMed, Cochrane Library, Web of Science, Scopus, and Embase databases. Two researchers searched for studies that met the inclusion criteria. In the univariate analysis, fixed- or random- effects models were used to obtain pooled estimates of the weighted mean difference (WMD) and odds ratio (OR) for risk factors. In the multivariate analysis, the ORs of the independent risk factors from each study were pooled after transforming the original estimates.
RESULTS
The meta-analysis included six studies. Univariate analysis showed that the following variables were statistically significant in MGRS: age (WMD = 1.78, 95%CI 0.21-3.35), hypertension (OR = 0.54, 95%CI 0.4-0.73), diabetes (OR = 0.42, 95%CI 0.29-0.59), albumin (WMD = - 0.26, 95%CI - 0.38--0.14), urinary protein level (WMD = 0.76, 95%CI 0.31-1.2), urinary protein ≥ 1.5 g/d (OR = 1.98, 95%CI 1.46-2.68), lambda-chain value (WMD = 29.02, 95%CI 16.55-41.49), abnormal free light-chain ratio (OR = 4.16, 95%CI 1.65-10.47), bone marrow puncture rate (OR = 5.11, 95% CI 1.31-19.95), and abnormal bone marrow outcome rate (OR = 9.63, 95%CI 1.98-46.88). Multivariate analysis showed urinary protein ≥ 1.5 g/d (OR = 2.80, 95%CI 1.53-5.15) and an abnormal free light-chain ratio (OR = 6.98, 95%CI 4.10-11.91) were associated with predictors of MGRS.
CONCLUSIONS
Compared with non-MGRS patients with monoclonal gammopathy and concomitant kidney diseases, patients with MGRS were older, had fewer underlying diseases, more urinary protein, more abnormal free light-chain ratio, and more abnormal bone marrow results. Urinary protein ≥ 1.5 g/d and an abnormal free light-chain ratio were independent risk factors for MGRS.
Topics: Humans; Paraproteinemias; Kidney; Monoclonal Gammopathy of Undetermined Significance; Kidney Diseases; Immunoglobulin Light Chains
PubMed: 38229028
DOI: 10.1186/s12882-024-03458-5 -
BMJ Open Jan 2024Multiple myeloma (MM) is a malignant plasma cell disorder. The most widely accepted staging system for MM is the revised International Staging System based on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Multiple myeloma (MM) is a malignant plasma cell disorder. The most widely accepted staging system for MM is the revised International Staging System based on cytogenetic and clinical biomarkers. The circulating clonal plasma cells (CPCs) were reported to have potential prognostic impact on MM. Among various diagnostic approaches, multiparametric flow cytometry (FCM) offers heightened sensitivity, minimal invasiveness and reproducibility. We conducted a meta-analysis to evaluate the prognostic value of quantifying CPCs via FCM in newly diagnosed symptomatic MM (NDMM) patients.
DESIGN
Systematic review and meta-analysis.
DATA SOURCE
PubMed, Web of Science, Embase and references of included studies.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
We included observational studies that evaluated the prognostic value of CPCs detected by FCM in NDMM.
DATA EXTRACTION AND SYNTHESIS
Data were screened and extracted independently by two investigators. The pooled results originated from random effects models. The primary endpoint was overall survival (OS). The secondary endpoint was progression-free survival (PFS). To evaluate the prognostic value of CPCs in NDMM, HRs and their 95% CI for both OS and PFS were derived using COX multivariable models. These values were then used to compute the pooled estimated effect.
RESULTS
Our meta-analysis encompassed a total of 2704 NDMM patients from 11 studies up to 27 August 2022. The pooled HR for OS and PFS in CPC-positive (CPCs+) group and CPC-negative group were 1.95 (95% CI 1.24 to 3.07) and 2.07 (95% CI 1.79 to 2.39), respectively. The autologous stem cell transplantation (ASCT) failed to eliminate the adverse impact on OS and PFS. The heterogeneity may stem from the use of novel agents or traditional chemotherapy as initial treatment.
CONCLUSION
This meta-analysis indicates CPCs+ had an adverse impact on the prognosis of NDMM patients in the total population, and the adverse impact could not be eliminated by ASCT.
PROSPERO REGISTRATION NUMBER
CRD42021272381.
Topics: Humans; Multiple Myeloma; Prognosis; Plasma Cells; Flow Cytometry; Hematopoietic Stem Cell Transplantation; Reproducibility of Results; Transplantation, Autologous
PubMed: 38216195
DOI: 10.1136/bmjopen-2022-071548 -
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