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Cancer Cell International Sep 2023In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the... (Review)
Review
BACKGROUND
In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the present study, we sought for conducting a systematic review and meta-analysis with the aim of evaluating the safety and efficacy of BsAbs in MM patients.
METHODS
PubMed, Scopus, Web of Science, and Embase databases were systematically searched on June 10, 2022. Two steps of title/abstract and full-text screening were performed for selecting the relevant articles. The primary endpoint was considered to evaluate the safety of BsAbs by examining the rate of hematologic and non-hematologic adverse effects (AEs). The secondary outcome was set at the efficacy of BsAbs through pooling objective response rate (ORR), (stringent) complete response (sCR/CR), very good partial response (VGPR), and partial response (PR).
RESULTS
Eleven publications with a total of nine evaluable BsAbs were included for qualitative and quantitative data synthesis. Hematologic AEs were more common among patients than non-hematologic events, with the most frequent events being anemia (41.4%), neutropenia (36.4%), and thrombocytopenia (26.3%). The most common non-hematological AE was infection, which occurred in 39.9% of patients, followed by dysgeusia (28.3%), fatigue (26.5%), and diarrhea (25.8%). Besides, 8.1% of patients experienced immune effector cell-associated neurotoxicity syndrome and neurotoxicity occurred in 5.1% of them. Moreover, 59.8% of patients experienced cytokine release syndrome. The pooled rate of deaths attributable to BsAbs was estimated at 0.1%. In terms of efficacy measures, the ORR was achieved in 62.6% of MM patients, and the pooled rates of sCR/CR, VGPR, and PR were 22.7%, 23.0%, and 12.1%, respectively.
CONCLUSIONS
In an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients. However, there is still room for developing BsAbs with a lower rate of AEs and capable of bypassing tumor evasion mechanisms.
PubMed: 37670301
DOI: 10.1186/s12935-023-03045-y -
Leukemia Research Reports 2017Multiple myeloma is a relatively uncommon plasma cell malignancy. Preclinical and clinical studies have suggested that aspirin might modify the risk of multiple myeloma.... (Review)
Review
Multiple myeloma is a relatively uncommon plasma cell malignancy. Preclinical and clinical studies have suggested that aspirin might modify the risk of multiple myeloma. We performed a systematic review and meta-analysis of studies to examine the association between regular aspirin use and risk of multiple myeloma. Five observational studies including 332,660 adults were evaluated. The pooled estimate had a hazard ratio of 0.90 (95% confidence interval =0.58-1.39; P=0.638). Odds ratios from the two case-control studies were similar. The findings demonstrated that there was no significant association between aspirin use and the risk of multiple myeloma.
PubMed: 28331798
DOI: 10.1016/j.lrr.2017.02.002 -
British Journal of Haematology Nov 2023Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy....
Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis.
Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.
PubMed: 37533165
DOI: 10.1111/bjh.19017 -
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 -
Leukemia & Lymphoma Jun 2021Clinical trials may be inconsistent in their enrollment and reporting of patients with multiple myeloma (MM) who have renal insufficiency (RI). We performed a systematic... (Meta-Analysis)
Meta-Analysis
Clinical trials may be inconsistent in their enrollment and reporting of patients with multiple myeloma (MM) who have renal insufficiency (RI). We performed a systematic review of all MM randomized clinical trials (RCT) from 2005-2019 to evaluate reporting of prevalence, eligibility criteria and outcomes of patients with RI and MM. One-hundred and twenty-three RCTs were included. Only 30% of studies clearly reported on the proportion of patients who had RI. Only 68.2% reported eligibility criteria pertaining to RI, with no uniformity in the reported criteria. The relative risk (RR) of disease progression or death in patients with RI was higher than those without, RR of 1.20 (1.003-1.431) for relapsed/refractory and 1.07 (1.001-1.046) for newly diagnosed. There is inconsistent reporting and enrollment of patients with RI on MM RCT's. We advocate for higher enrollment of patients with RI and transparent reporting of their eligibility criteria and outcomes.
Topics: Humans; Multiple Myeloma; Randomized Controlled Trials as Topic; Renal Insufficiency
PubMed: 33416412
DOI: 10.1080/10428194.2020.1867725 -
PloS One 2013In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a meta-analysis of RCTs examining the efficacy and safety of lenalidomide for MM.
PATIENTS AND METHODS
Databases were searched using the terms "lenalidomide or revlimid AND multiple myeloma."RCTs evaluating initial or maintenance therapeutic outcomes were included. Main outcome measures were response rates, progression-free survival (PFS), overall survival, and adverse events.
RESULTS
Seven trials were included (N = 192-614 participants). Lenalidomide doses and treatment regimens differed between trials. Complete response (CR) and very good partial response (VGPR) risk ratios (RR) favored lenalidomide over placebo (CR = 2.54, 95% confidence interval [CI] = 1.29-5.02; VGPR = 2.82, 95% CI = 1.30-6.09). The PFS hazard ratio favored lenalidomide over placebo (0.37, 95% CI = 0.33-0.41). For adverse events, neutropenia, deep vein thrombosis (DVT), infection, and hematologic cancer RR favored placebo over lenalidomide (neutropenia: 4.74, 95% CI = 2.96-7.57; DVT: 2.52; 95% CI: 1.60-3.98; infection: 1.98; 95% CI: 1.50-2.62; hematologic cancer: 3.20; 95% CI: 1.28-7.98).
CONCLUSIONS
Lenalidomide is an effective treatment for MM; however, treatment-related adverse events must be considered and appropriate adjustments and/or prophylactic treatment should be initiated where possible.
Topics: Disease-Free Survival; Humans; Lenalidomide; Multiple Myeloma; Neoplasms, Second Primary; Randomized Controlled Trials as Topic; Thalidomide; Treatment Outcome
PubMed: 23691202
DOI: 10.1371/journal.pone.0064354 -
BMC Cancer Jun 2021Patients with multiple myeloma (MM) remain at an increased risk of infection due to the disease process, as well as the ensuing treatments. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with multiple myeloma (MM) remain at an increased risk of infection due to the disease process, as well as the ensuing treatments.
METHODS
We performed a systematic review to evaluate the monthly risk of grade III/IV infection, pneumonia, and neutropenia in patients with myeloma enrolled in randomized clinical trials (RCTs).
RESULTS
The risk of grade III or higher infection, pneumonia, and neutropenia persists among all phases of treatment. There was no statistical difference in grade III or higher infection, pneumonia, and neutropenia between frontline and relapsed/refractory setting. In the maintenance setting, the complications of infection, pneumonia, and neutropenia were low, but not negligible. Three-drug regimens were no more likely than two-drug regimens to have an increased risk of Grade III or higher infection.
CONCLUSIONS
This is the first study to quantify the monthly risk of grade III or higher infection, pneumonia, and neutropenia across different treatment regimens in the frontline, maintenance, and relapsed/refractory settings. The results of our systematic review demonstrate a significant risk for severe infection, pneumonia, and neutropenia in patients with MM. Further studies are needed to determine the value of antibiotic prophylaxis in a broader myeloma patient population, as well as other approaches that will further mitigate the morbidity and mortality related to infection in this vulnerable patient population.
Topics: History, 21st Century; Humans; Infections; Multiple Myeloma; Risk Factors
PubMed: 34172037
DOI: 10.1186/s12885-021-08451-x -
European Journal of Haematology Dec 2022Hematological malignancies represent defying clinical conditions, with high levels of morbidity and mortality, particularly considering patients who manifest multiple... (Review)
Review
Hematological malignancies represent defying clinical conditions, with high levels of morbidity and mortality, particularly considering patients who manifest multiple refractory diseases. Recently, chimeric antigen receptor (CAR)-T cell therapy has emerged as a potential treatment option for relapsed/refractory B cell malignancies, which have motivated the Food and Drug Administration approval of a series of products based on this technique. The objective of this systematic review was to assess the efficacy and safety of CAR-T cell therapy for patients with hematological malignancies. A comprehensive literature search was conducted in the electronic databases (CENTRAL, Embase, LILACS, and MEDLINE), clinical trials register platforms (Clinicaltrials.gov and WHO-ICTRP), and grey literature (OpenGrey). The Cochrane Handbook for Reviews of Interventions was used for developing the review and the PRISMA Statement for manuscript reporting. The protocol was prospectively published in PROSPERO database (CRD42020181047). After the selection process, seven RCTs were included, three of which with available outcome results. The available results are from studies assessing axicabtagene, lisocabtagene, and tisagenlecleucel for patients with B cell lymphoma, and the certainty of evidence ranged from very low to low for survival and progression-related outcome and for safety outcomes. Additionally, four randomized controlled trials comparing CAR-T cell therapy to the standard treatment for various types of relapsed/refractory B cell non-Hodgkin lymphomas and multiple myeloma included in this systematic review still did not have available outcome data. The results of this review may be used to guide clinical practice but evidence concerning the safety and efficacy of CAR-T Cell therapy for hematological malignancies is still immature to recommend its application outside of clinical trials or compassionate use context for advanced and terminal cases. It is expected the results of the referred comparative studies will provide further elements to subsidize the broader application of this immunotherapy.
Topics: Humans; Receptors, Chimeric Antigen; Neoplasm Recurrence, Local; Immunotherapy, Adoptive; Hematologic Neoplasms; Lymphoma, B-Cell; Cell- and Tissue-Based Therapy
PubMed: 36018500
DOI: 10.1111/ejh.13851 -
Journal of Musculoskeletal & Neuronal... Dec 2022Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM)... (Meta-Analysis)
Meta-Analysis Review
Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM) patients. The NCBI PubMed, Web of Science, Scopus and ClinicalTrials.gov databases, were systematically searched for interventional studies, assessing the use of BP and DENOS in MM patients. Overall survival, disease progression, skeletal-related events, bone pain, osteonecrosis of the jaw (ONJ) and renal toxicity were the outcomes of interest. A total of 993 studies were retrieved and 43 were used for qualitative synthesis. Clodronate (CLOD) and zoledronic acid (ZOL) were effective in reducing skeletal complications compared to placebo. Results are mixed regarding the efficacy of pamidronate in reducing skeletal related events. ONJ rates were higher for ZOL, but under 5%, with CLOD having the safest profile. DENOS demonstrated non-inferiority to ZOL, in improving overall survival [pooled Hazard Ratio(HR) 1.02(95% CI 0.72,1.44)], progression free survival [pooled HR 0.92(95% CI 0.76,1.11)] and in reducing skeletal related events [pooled HR 1.03(95% CI 0.92,1.16)], with similar rates of ONJ and better safety profile regarding renal toxicity. Denosumab has comparable efficacy and safety with ZOL and may even replace BPs in the future, in the management of myeloma bone disease.
Topics: Humans; Diphosphonates; Multiple Myeloma; Denosumab; Zoledronic Acid; Clodronic Acid
PubMed: 36458395
DOI: No ID Found -
Translational Cancer Research Mar 2023This study sought to investigate the clinical characteristics and prognosis of thromboembolism in multiple myeloma (MM).
BACKGROUND
This study sought to investigate the clinical characteristics and prognosis of thromboembolism in multiple myeloma (MM).
METHODS
The PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were systematically searched to retrieve relevant articles from the establishment of the databases to May 2022. This meta-analysis was performed to investigate the relationship between thromboembolism and overall survival (OS), progression-free survival (PFS), event-free survival (EFS), and mortality in MM patients. The meta-analysis of the included studies was performed using Revman5.3 software after quality evaluation.
RESULTS
A total of 9 studies from 7 articles, which included 38,047 MM patients and 6,412 cases of thromboembolism in the analysis. The levels of β2 microglobulin affected the occurrence of thromboembolism in MM patients [standard mean difference (SMD) =-0.09, 95% confidence interval (CI): -0.18 to -0.01, P=0.02]. Venous thromboembolism (VTE) predicted poorer OS [hazard ratio (HR) = 0.79, 95% CI: 0.64-0.98, P=0.03] and higher early mortality (HR =2.27, 95% CI: 1.26-4.08, P=0.006) in MM. There was no significant difference in PFS/EFS (HR =0.81, 95% CI: 0.64-1.01, P=0.06) between thrombosis/embolism and non-thrombotic embolism. Arterial thrombosis was associated with significantly higher risk of death at 5 years (HR =1.89, 95% CI: 1.33-2.69, P<0.01).
CONCLUSIONS
β2 microglobulin levels were associated with VTE in MM. MM patients with VTE were more likely to have poorer prognosis and higher mortality rate than those without VTE. MM patients with arterial thromboembolism had higher 5-year mortality rate than those without arterial thromboembolism.
PubMed: 37033347
DOI: 10.21037/tcr-23-285