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Annals of Medicine Dec 2024Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.
METHODS
The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software.
RESULTS
Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, < 0.001).
CONCLUSION
Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.
Topics: Humans; Multiple Myeloma; Plasma Cells; Prognosis; Biomarkers; Proportional Hazards Models
PubMed: 38599340
DOI: 10.1080/07853890.2024.2338604 -
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 -
Frontiers in Oncology 2024Since no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD)...
BACKGROUND
Since no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD) in the frontline treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM), this study systematically reviewed the clinical studies regarding immunotherapy with daratumumab and RVD regimen in the treatment of TIE-NDMM to explore the optimization direction of the best first-line therapy.
METHODS
The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to collect studies on regimens containing daratumumab or RVD/RVD-lite for TIE-NDMM. Pooled and meta-analysis was then performed to compare the overall response rate (ORR), stringent complete remission (sCR) and CR rate, progression-free survival (PFS), overall survival (OS) and treatment-related discontinuation rate between daratumumab-containing immunotherapy regimen and RVD/RVD-lite regimen by using R 4.3.1 software.
RESULTS
Nine prospective clinical trials were included, including 1795 TIE-NDMM or NDMM without intent for immediate ASCT. Among them, 938 patients were treated with daratumumab-based immunotherapy and 857 with RVD/RVD-lite regimens. Meta-analysis results showed that The daratumumab-based regimen showed a significantly higher CR/sCR rate than RVD/RVD-lite for TIE-NDMM (47% vs. 24%, P<0.01). The median PFS of the daratumumab-based and RVD/RVD-lite groups were 52.6 months and 35.1 months respectively (HR 0.77, 95%CI, 0.66-0.90). The median OS of both groups was not reached, and there were no significant differences in OS between the two groups (HR 1.03, 95%CI, 0.86-1.23). The therapy discontinuation rate led by adverse events was significantly higher in the RVD/RVD-lite group than in the daratumumab-based regimen group for the TIE-NDMM (16% vs. 7%, P=0.03).
CONCLUSION
This meta-analysis suggests that daratumumab-containing immunotherapy is superior to RVD in the depth of treatment efficacy, progression-free survival, and lower treatment-related discontinuation rates. Limited by the lack of head-to-head clinical trials, this conclusion needs to be verified by concurrent cohort studies.
PubMed: 38333688
DOI: 10.3389/fonc.2024.1286029 -
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 -
Journal of Craniovertebral Junction &... 2023Multiple Myeloma is a B-cell malignancy which can cause variety of lesions of the spine and spinal cord. The management of patients with spinal cord compression (SCC),... (Review)
Review
BACKGROUND
Multiple Myeloma is a B-cell malignancy which can cause variety of lesions of the spine and spinal cord. The management of patients with spinal cord compression (SCC), and the efficacy and security of minimally invasive therapeutic approaches, are the main topics of discussion.
METHODS
To systematically review the scientific literature on neurosurgical aspects of MM spinal cord lesion management, a search was conducted among scientific papers in the databases ScienceDirect, Cochrane Library, and PubMed using keywords and Boolean operators. These comprise MM and lesions of the spine and spinal cord. Each database was searched from the earliest available article to January 2017.
RESULTS
According to the literature, low-dose radiotherapy, antimyeloma medications, and bisphosphonates comprise the mainstay management for symptomatic spinal lesions. The decision to operation is based on presence of myelopathy and degree of spinal cord compression.
CONCLUSIONS
As a result of the analysis, the following conclusions may be drawn: (1) surgery is a valuable option for MM patients with symptomatic spinal involvement who experience rapid neurological deterioration with SCC and/or mechanical instability and (2) it is important to ensure that the benefits of surgical treatment outweigh the risks, as patients with MM are susceptible to infections.
PubMed: 38268680
DOI: 10.4103/jcvjs.jcvjs_111_23 -
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 -
Frontiers in Oncology 2023The current study aims to evaluate the safety and efficacy of anti-CD38 monoclonal antibodies (mAbs) among patients with relapsed/refractory multiple myeloma (RRMM)...
Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.
OBJECTIVES
The current study aims to evaluate the safety and efficacy of anti-CD38 monoclonal antibodies (mAbs) among patients with relapsed/refractory multiple myeloma (RRMM) through meta-analysis.
METHODS
As of June 2023, we searched PubMed, Web of Science, Embase and the Cochrane Library. Randomized controlled trials (RCTs) which compared the clinical outcomes of anti-CD38 mAbs plus immunomodulatory drugs (IMiDs) or proteasome inhibitors (PIs) plus dexamethasone and IMiDs (or PIs) and dexamethasone alone for RRMM patients were included. Efficacy outcomes were mainly evaluated with progression-free survival (PFS) and overall survival (OS). The safety was analyzed with hematologic and nonhematologic treatment-emergent adverse events (TEAEs). All results were pooled using hazard ratio (HR), relative risk (RR), and their 95% confidence interval (CI) and prediction interval (PI).
RESULTS
This meta-analysis included 11 RCTs in total. Compared with IMiDs (or PIs) and dexamethasone alone, anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone significantly prolonged PFS (HR: 0.552, 95% CI = 0.461 to 0.659, 95% PI = 0.318 to 0.957) and OS (HR: 0.737, 95% CI = 0.657 to 0.827, 95% PI = 0.626 to 0.868) in patients with RRMM. Additionally, RRMM patients receiving anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone achieved higher rates of overall response (RR: 1.281, 95% CI = 1.144 to 1.434, 95% PI = 0.883 to 1.859), complete response or better (RR: 2.602, 95% CI = 1.977 to 3.424, 95% PI = 1.203 to 5.628), very good partial response (VGPR) or better (RR: 1.886, 95% CI = 1.532 to 2.322, 95% PI = 0.953 to 3.731), and minimum residual disease (MRD)-negative (RR: 4.147, 95% CI = 2.588 to 6.644, 95% PI = 1.056 to 16.283) than those receiving IMiDs (or PIs) and dexamethasone alone. For TEAEs, the rates of hematologic and nonhematologic TEAEs, including thrombocytopenia, neutropenia, upper respiratory tract infection (URTI), pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension, were higher in the anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone group than in the IMiDs (or PIs) and dexamethasone group.
CONCLUSION
Our study showed that anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone improved PFS and OS, and achieved higher rates of overall response, complete response or better, VGPR or better, and MRD-negative, as well as higher rates of thrombocytopenia, neutropenia, URTI, pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension in RRMM patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023431071.
PubMed: 38144527
DOI: 10.3389/fonc.2023.1240318 -
Life (Basel, Switzerland) Nov 2023Over the last decade, many studies have assessed the efficacy of treatments for refractory/relapsed multiple myeloma (R/R MM). While combination therapies show greater... (Review)
Review
BACKGROUND
Over the last decade, many studies have assessed the efficacy of treatments for refractory/relapsed multiple myeloma (R/R MM). While combination therapies show greater efficacy than traditional methods, limited research has targeted elderly patients who might be less resilient to treatments. Our study aimed to evaluate treatment efficacy for these elderly patients.
METHODS
We carried out a comprehensive review of the literature using a systematic approach. Initially, 4966 citations were retrieved and subsequently narrowed down to 13 eligible randomized controlled trials (RCTs) through our systematic review process from databases like Embase, PubMed, and Cochrane Library from 1 January 2000 to 31 December 2022. Evidence was collated through a frequentist network meta-analysis, using the hazard ratio (HR) for evaluation.
RESULTS
Combined therapy of daratumumab, lenalidomide, and dexamethasone (DaraLenDex) was the preferred treatment for R/R MM elderly patients. Its strengths included an HR for progression-free survival (0.15; 95% CI: 0.09-0.25) and a 96% P-score.
CONCLUSIONS
Our analysis suggests that, pending more comprehensive RCTs, DaraLenDex is the treatment with the highest efficacy for R/R MM in elderly patients.
PubMed: 38137860
DOI: 10.3390/life13122259 -
Cancers Dec 2023Although chimeric antigen receptor (CAR)-T cell therapies are typically administered in the inpatient setting, outpatient administration is rapidly expanding. However,... (Review)
Review
The Impact of Outpatient versus Inpatient Administration of CAR-T Therapies on Clinical, Economic, and Humanistic Outcomes in Patients with Hematological Cancer: A Systematic Literature Review.
Although chimeric antigen receptor (CAR)-T cell therapies are typically administered in the inpatient setting, outpatient administration is rapidly expanding. However, there is limited summarized evidence comparing outcomes between outpatient and inpatient administration. This systematic literature review aims to compare the safety, efficacy, quality of life (QoL), costs, and healthcare resource utilization (HCRU) outcomes in patients with hematological cancer who are administered CAR-T therapy in an outpatient versus an inpatient setting. Publications (2016 or later) that reported the outcomes of interest in patients treated with a CAR-T therapy in both outpatient and inpatient settings, or only the outpatient setting, were reviewed. In total, 38 publications based on 21 studies were included. Safety findings suggested the comparable frequency of adverse events in the two settings. Eleven studies that reported data in both settings showed comparable response rates (80-82% in outpatient and 72-80% in inpatient). Improvements in the QoL were observed in both settings while costs associated with CAR-T therapy were lower in the outpatient setting. Although unplanned hospitalizations were higher in the outpatient cohort, overall HCRU was lower. Outpatient administration of CAR-T therapy appears to have comparable outcomes in safety, efficacy, and QoL to inpatient administration while reducing the economic burden.
PubMed: 38136292
DOI: 10.3390/cancers15245746