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Journal of Pain Research 2024Peripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal... (Review)
Review
BACKGROUND
Peripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN. This study aimed to conduct a comprehensive analysis of the literature to assess the effectiveness and safety of acupuncture as a treatment for MMPN.
METHODS
The PubMed, Web of Science, MEDLINE, Cochrane Library, and Embase databases were comprehensively searched from inception to November 1, 2023 to identify relevant studies pertaining to the use of acupuncture to treat MMPN.
RESULTS
A total of five studies, encompassing 97 patients diagnosed with drug-related PN, were ultimately included in this analysis. The literature lacks any reports pertaining to the utilization of acupuncture for disease-related PN. ST36, LI4, SP6, and EX-LE-10 were found to be the most frequently chosen acupoints. Following acupuncture treatment, there was a consistent reduction in scores on the Visual Analogue Scale (VAS), Neuropathic Pain Scale (NPS), Brief Pain Inventory-Short Form (BPI-SF), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) among MMPN patients. The results of Nerve Conduction Velocity (NCV) tests yielded conflicting results. No severe adverse effects were reported.
CONCLUSION
The use of acupuncture for disease-related PN has not been studied to date. Acupuncture is safe for drug-related PN and is helpful for relieving pain. But uncertainty exists regarding the efficacy of this approach because there is substantial heterogeneity with respect to acupuncture treatment regimens, and more high-quality studies on this topic are warranted.
PubMed: 38699068
DOI: 10.2147/JPR.S448634 -
Blood Advances Jul 2024
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Clinical Trials as Topic; Immunoglobulin Light Chains
PubMed: 38696707
DOI: 10.1182/bloodadvances.2024012737 -
The Cochrane Database of Systematic... May 2024Multiple myeloma (MM) is a haematological malignancy that is characterised by proliferation of malignant plasma cells in the bone marrow. For adults ineligible to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple myeloma (MM) is a haematological malignancy that is characterised by proliferation of malignant plasma cells in the bone marrow. For adults ineligible to receive high-dose chemotherapy and autologous stem cell transplant, the recommended treatment combinations in first-line therapy generally consist of combinations of alkylating agents, immunomodulatory drugs, and proteasome inhibitors. Daratumumab is a CD38-targeting, human IgG1k monoclonal antibody recently developed and approved for the treatment of people diagnosed with MM. Multiple myeloma cells uniformly over-express CD-38, a 46-kDa type II transmembrane glycoprotein, making myeloma cells a specific target for daratumumab.
OBJECTIVES
To determine the benefits and harms of daratumumab in addition to antineoplastic therapy compared to antineoplastic therapy only for adults with newly diagnosed MM who are ineligible for transplant.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, EU Clinical Trials Register, ClinicalTrials.gov, WHO ICTRP, and conference proceedings from 2010 to September 2023.
SELECTION CRITERIA
We included randomised controlled trials that compared treatment with daratumumab added to antineoplastic therapy versus the same antineoplastic therapy alone in adult participants with a confirmed diagnosis of MM. We excluded quasi-randomised trials and trials with less than 80% adult participants, unless there were subgroup analyses of adults with MM.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the results of the search strategies for eligibility. We documented the process of study selection in a flowchart as recommended by the PRISMA statement. We evaluated the risk of bias in included studies with RoB 1 and assessed the certainty of the evidence using GRADE. We followed standard Cochrane methodological procedures.
MAIN RESULTS
We included four open-label, two-armed randomised controlled trials (34 publications) involving a total of 1783 participants. The ALCYONE, MAIA, and OCTANS trials were multicentre trials conducted worldwide in middle- and high-income countries. The AMaRC 03-16 trial was conducted in one high-income country, Australia. The mean age of participants was 69 to 74 years, and the proportion of female participants was between 40% and 54%. All trials evaluated antineoplastic therapies with or without daratumumab. In the ALCYONE and OCTANS trials, daratumumab was combined with bortezomib and melphalan-prednisone. In the AMaRC 03-16 study, it was combined with bortezomib, cyclophosphamide, and dexamethasone, and in the MAIA study, it was combined with lenalidomide and dexamethasone. None of the included studies was blinded (high risk of performance and detection bias). One study was published as abstract only, therefore the risk of bias for most criteria was unclear. The other three studies were published as full texts. Apart from blinding, the risk of bias was low for these studies. Overall survival Treatment with daratumumab probably increases overall survival when compared to the same treatment without daratumumab (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.53 to 0.76, 2 studies, 1443 participants, moderate-certainty evidence). After a follow-up period of 36 months, 695 per 1000 participants survived in the control group, whereas 792 per 1000 participants survived in the daratumumab group (95% CI 758 to 825). Progression-free survival Treatment with daratumumab probably increases progression-free survival when compared to treatment without daratumumab (HR 0.48, 95% CI 0.39 to 0.58, 3 studies, 1663 participants, moderate-certainty evidence). After a follow-up period of 24 months, progression-free survival was reached in 494 per 1000 participants in the control group versus 713 per 1000 participants in the daratumumab group (95% CI 664 to 760). Quality of life Treatment with daratumumab may result in a very small increase in quality of life after 12 months, evaluated on the EORTC QLQ-C30 global health status scale (GHS), when compared to treatment without daratumumab (mean difference 2.19, 95% CI -0.13 to 4.51, 3 studies, 1096 participants, low-certainty evidence). The scale is from 0 to 100, with a higher value indicating a better quality of life. On-study mortality Treatment with daratumumab probably decreases on-study mortality when compared to treatment without daratumumab (risk ratio (RR) 0.72, 95% CI 0.62 to 0.83, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 366 per 1000 participants in the control group and 264 per 1000 participants in the daratumumab group died (95% CI 227 to 304). Serious adverse events Treatment with daratumumab probably increases serious adverse events when compared to treatment without daratumumab (RR 1.18, 95% CI 1.02 to 1.37, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 505 per 1000 participants in the control group versus 596 per 1000 participants in the daratumumab group experienced serious adverse events (95% CI 515 to 692). Adverse events (Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3) Treatment with daratumumab probably results in little to no difference in adverse events (CTCAE grade ≥ 3) when compared to treatment without daratumumab (RR 1.01, 95% CI 0.99 to 1.02, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 953 per 1000 participants in the control group versus 963 per 1000 participants in the daratumumab group experienced adverse events (CTCAE grade ≥ 3) (95% CI 943 to 972). Treatment with daratumumab probably increases the risk of infections (CTCAE grade ≥ 3) when compared to treatment without daratumumab (RR 1.52, 95% CI 1.30 to 1.78, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 224 per 1000 participants in the control group versus 340 per 1000 participants in the daratumumab group experienced infections (CTCAE grade ≥ 3) (95% CI 291 to 399).
AUTHORS' CONCLUSIONS
Overall analysis of four studies showed a potential benefit for daratumumab in terms of overall survival and progression-free survival and a slight potential benefit in quality of life. Participants treated with daratumumab probably experience increased serious adverse events. There were likely no differences between groups in adverse events (CTCAE grade ≥ 3); however, there are probably more infections (CTCAE grade ≥ 3) in participants treated with daratumumab. We identified six ongoing studies which might strengthen the certainty of evidence in a future update of this review.
Topics: Adult; Aged; Female; Humans; Middle Aged; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bias; Bortezomib; Multiple Myeloma; Progression-Free Survival; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38695605
DOI: 10.1002/14651858.CD013595.pub2 -
Clinical Genitourinary Cancer Jun 2024To provide an updated view on the role of cell-free DNA as a predictor of pathological response to neoadjuvant therapy in patients with muscle-invasive bladder cancer. (Review)
Review
OBJECTIVE
To provide an updated view on the role of cell-free DNA as a predictor of pathological response to neoadjuvant therapy in patients with muscle-invasive bladder cancer.
METHODS
A systematic review was conducted from September 2023 to October 2023. Selected studies from the MEDLINE and clinical trial databases were critically analyzed regarding the clinical efficacy of cell-free DNA as a predictive instrument after neoadjuvant therapy in bladder cancer. The methodological quality assessment was based on the QUADAS-2 tool.
RESULTS
In this systematic review, we analyzed 5 studies encompassing a cumulative patient cohort of 780 individuals diagnosed with muscle-invasive bladder cancer, with a median follow-up ranging from 6 to 23 months. Among these studies, 4 primarily focused on detecting and analyzing circulating tumor DNA in plasma, while 1 study uniquely utilized cell-free tumor DNA in urine samples. The diagnostic accuracy of cell-free DNA in plasma ranges from 79% to 100%, indicating a variable yet significant predictive capability. In contrast, the study utilizing urinary cell-free DNA demonstrated an accuracy of 81% in predicting treatment response post-neoadjuvant chemotherapy.
CONCLUSION
Cell-free DNA is emerging as a valuable biomarker for predicting response to neoadjuvant chemotherapy in patients with muscle-invasive bladder tumors.
Topics: Urinary Bladder Neoplasms; Humans; Neoadjuvant Therapy; Biomarkers, Tumor; Circulating Tumor DNA; Treatment Outcome; Prognosis
PubMed: 38688207
DOI: 10.1016/j.clgc.2024.102087 -
Hematology (Amsterdam, Netherlands) Dec 2024To evaluate whether patients with multiple myeloma (MM) could benefit from tandem autologous hematopoietic stem cell transplantation (auto-HSCT), PubMed, Embase, Web of... (Meta-Analysis)
Meta-Analysis
To evaluate whether patients with multiple myeloma (MM) could benefit from tandem autologous hematopoietic stem cell transplantation (auto-HSCT), PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched, and 10 eligible studies were included after data extraction and quality evaluation. Meta-analysis showed that compared to single autologous hematopoietic stem cell transplantation, tandem auto-HSCT does not improve OS, EFS or efficacy in MM patients, and may even lead to higher treatment-related mortality (TRM). MM patients who received autologous tandem allogeneic HSCT did not achieve better response compared to tandem autologous HSCT. In summary, compared to single autologous hematopoietic stem cell transplantation, tandem autologous hematopoietic stem cell transplantation cannot provide survival advantages for MM patients, and MM patients cannot benefit from autologous tandem allogeneic hematopoietic stem cell transplantation.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Multiple Myeloma; Transplantation, Autologous
PubMed: 38651865
DOI: 10.1080/16078454.2024.2343164 -
Frontiers in Oncology 2024The low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are...
BACKGROUND
The low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are yet to be optimized. The combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high clinical efficacy in several clinical trials for RRMM. We here conducted a meta-analysis to confirm its efficacy and safety.
METHODS
We collected data from Embase, Web of Science, PubMed, CNKI, Wanfang and Cochrane databases up to April 2023. We extracted and evaluated data related to the efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapies in RRMM patients. The data was then analyzed using RevMan5.4 and StataSE-64 software. PROSPERO number was CRD42023455002.
RESULTS
Our meta-analysis included 12 relevant clinical trials involving 347 RRMM patients who were treated with combined anti-BCMA and anti-CD19 CAR-T cell therapies. For efficacy assessment, the pooled overall response rate (ORR) was 94% (95% CI: 91%-98%), the complete response rate (CRR) was 50% (95% CI: 29%-71%), and the minimal residual disease (MRD) negativity rate within responders was 73% (95% CI: 66%-80%). In terms of safety, the pooled all-grade cytokine release syndrome (CRS) rate was 98% (95% CI: 97%-100%), grade≥3 CRS rate was 9% (95% CI: 4%-14%), and the incidence of neurotoxicity was 8% (95% CI: 4%-11%). Of hematologic toxicity, neutropenia was 82% (95% CI: 75%-89%), anemia was 71% (95% CI: 53%-90%), thrombocytopenia was 67% (95% CI: 40%-93%) and infection was 42% (95% CI: 9%-76%). The median progression-free survival (PFS) was 12.97 months (95% CI: 6.02-19.91), and the median overall survival (OS) was 26.63 months (95% CI: 8.14-45.11).
CONCLUSIONS
As a novel immunotherapy strategy with great potential, the combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high efficacy in RRMM, but its safety needs further improvement. This meta-analysis suggests possible optimization of combined CAR-T therapy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023455002.
PubMed: 38651157
DOI: 10.3389/fonc.2024.1355643 -
CytoJournal 2024Multiple myeloma (MM) is a bone marrow cancer that profoundly affects plasma cells involved in the immune response. Myeloma cells alter the average production of cells...
OBJECTIVE
Multiple myeloma (MM) is a bone marrow cancer that profoundly affects plasma cells involved in the immune response. Myeloma cells alter the average production of cells in the bone marrow. Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy allows genetic modifications of an individual's T-cells to increase the expression of CARs used to identify and attach BCMA proteins to the malignant cells. Our main objective is to perform a systematic review and meta-analysis to explore the efficacy and safety of anti-BCMA CAR T-cell therapy for MM.
MATERIAL AND METHODS
We searched five databases, PubMed, CNKI, EMBASE, Cochrane, Web of Science, and CNKI, for studies published on anti-BCMA,CAR-T-cell treatment for MM. Inclusion criteria involved prospective single-arm studies either single or multi-center, in various MM phases and studies that reported anti-BCMA,CAR-T-cell treatment for MM. We excluded non-English publications and conference papers. All statistical analyses were performed in R software and Review Manager 5.4.1.
RESULTS
Thirteen articles were included in the analysis. We found that the overall response survival complete response increase was statistically significant. Similarly, the reduction in cytokine release syndrome grades 3 and 4 and neurotoxicity after follow-up was statistically significant. However, the reduction in minimal residual disease negativity (MRDN) was not statistically significant.
CONCLUSION
Using anti-BCMA CAR T-cell therapy in MM was highly efficacious and safe in lowering the adverse outcomes and improving the survival outcomes, complete response, and overall response.
PubMed: 38628287
DOI: 10.25259/Cytojournal_64_2023 -
Minimal residual disease in systemic light chain amyloidosis: a systematic review and meta-analysis.Journal of Cancer Research and Clinical... Apr 2024Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains... (Meta-Analysis)
Meta-Analysis
PURPOSE
Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains controversial, and this systematic review and meta-analysis aims to fill this gap.
METHODS
We searched for relevant studies on Pubmed, Embase, and Cochrane Controlled Register of Trials, nine studies involving 451 patients were included and meta-analyzed. This systematic review has been registered in PROSPERO (CRD42023494169).
RESULTS
Our study found that in the group of patients who achieved very good partial response (VGPR) or better, MRD negativity was correlated with higher cardiac and renal response rates [pooled risk ratio (RR) = 0.74 (95% CI 0.62-0.89), 0.74 (95% CI 0.64-0.87), respectively]. Patients with MRD positivity had a higher hematologic progression rate within two years after MRD detection [pooled RR = 10.31 (95% CI 2.02-52.68)]; and a higher risk of hematologic + organ progression in the first year [pooled RR = 12.57 (95% CI 1.73-91.04)]. Moreover, MRD negativity was correlated with a better progression-free survival (PFS) [pooled hazard ratio (HR) = 0.27 (95% CI 0.17-0.45)]; but it did not significantly improve the overall survival (OS) [pooled HR = 0.34 (95% CI 0.11-1.07)].
CONCLUSION
In AL amyloidosis, our study supports that MRD negativity correlates with higher cardiac or renal response rates and indicates a better PFS in the follow-up. However, the correlation between OS and the status of MRD is not significant.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Neoplasm, Residual; Amyloidosis; Hematologic Neoplasms; Kidney
PubMed: 38619663
DOI: 10.1007/s00432-024-05733-2 -
International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
American Journal of Hematology Jul 2024In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis.
In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis comparing the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/lenalidomide/dexamethasone (VRd). Three studies totaling 1597 patients (50% KRd-treated, 50% VRd-treated) were included. Despite similar survival outcomes and overall response rate compared with the VRd arm, KRd-treated subjects showed higher odds of achieving complete responses and measurable residual disease negativity. Among patients with high-risk cytogenetics (n = 348), KRd was associated with significant improvement in progression-free survival (HR = 0.70; 95% CI = 0.50-0.97; p = .03; I = 0%), suggesting carfilzomib-based induction may be preferable in this NDMM subpopulation.
Topics: Multiple Myeloma; Humans; Lenalidomide; Dexamethasone; Oligopeptides; Bortezomib; Antineoplastic Combined Chemotherapy Protocols; Progression-Free Survival; Treatment Outcome
PubMed: 38606993
DOI: 10.1002/ajh.27314