Maintenance Treatment for Patients With Mantle Cell Lymphoma: A Systematic Review and Meta-analysis of Randomized Trials.
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ABSTRACT:
SUBMITTER: Vidal L
PROVIDER: S-EPMC6745999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Maintenance rituximab in mantle cell lymphoma (MCL) has improved survival and supports exploration of maintenance with novel agents. We evaluated the safety and efficacy of ibrutinib maintenance (I-M) after induction in patients with treatment-naive MCL. Patients with MCL with complete response (CR) or partial response to frontline chemoimmunotherapy ± autologous stem cell transplantation (auto-SCT) received I-M 560 mg daily for up to 4 years. Primary objective was 3-year progression-free survival (PFS) rate from initiation of I-M. Minimal residual disease (MRD) assessments by next-generation sequencing (NGS) on peripheral blood were measured before I-M initiation and at 1, 6, and 18 to 24 months after initiation. Among 36 patients, the median age was 60 years (range, 46-90). For frontline treatment, 18 patients (50%) had consolidation with auto-SCT in CR1 before I-M. At median follow-up of 55.7 months, 17 patients (47%) completed full course I-M (median, 37.5 cycles; range, 2-52). The 3-year PFS and overall survival (OS) rates were 94% and 97%, respectively. With prior auto-SCT, 3-year PFS and OS rates were both 100%. The most common treatment-related adverse event with I-M was infection (n = 31; 86%), typically low grade; the most common grade 3/4 toxicities were hematologic. In 22 patients with MRD assessments, all were MRD negative after induction. Six became MRD positive on I-M, with 2 reverting to MRD-negative status with continued I-M, and all maintain radiographic CR with the exception of 1 with disease progression. I-M is feasible in MCL after frontline chemoimmunotherapy with manageable toxicities although significant. Changes in NGS-MRD were noted in limited patients during maintenance with few progression and survival events. This trial was registered at www.clinicaltrials.gov as #NCT02242097.
| S-EPMC10726243 | biostudies-literature
Project description:Osteopathic manipulative treatment (OMT) is a distinctive modality commonly used by osteopathic physicians to complement their conventional treatment of musculoskeletal disorders. Previous reviews and meta-analyses of spinal manipulation for low back pain have not specifically addressed OMT and generally have focused on spinal manipulation as an alternative to conventional treatment. The purpose of this study was to assess the efficacy of OMT as a complementary treatment for low back pain.Computerized bibliographic searches of MEDLINE, EMBASE, MANTIS, OSTMED, and the Cochrane Central Register of Controlled Trials were supplemented with additional database and manual searches of the literature. Six trials, involving eight OMT vs control treatment comparisons, were included because they were randomized controlled trials of OMT that involved blinded assessment of low back pain in ambulatory settings. Data on trial methodology, OMT and control treatments, and low back pain outcomes were abstracted by two independent reviewers. Effect sizes were computed using Cohen's d statistic and meta-analysis results were weighted by the inverse variance of individual comparisons. In addition to the overall meta-analysis, stratified meta-analyses were performed according to control treatment, country where the trial was conducted, and duration of follow-up. Sensitivity analyses were performed for both the overall and stratified meta-analyses.Overall, OMT significantly reduced low back pain (effect size, -0.30; 95% confidence interval, -0.47 - -0.13; P = .001). Stratified analyses demonstrated significant pain reductions in trials of OMT vs active treatment or placebo control and OMT vs no treatment control. There were significant pain reductions with OMT regardless of whether trials were performed in the United Kingdom or the United States. Significant pain reductions were also observed during short-, intermediate-, and long-term follow-up.OMT significantly reduces low back pain. The level of pain reduction is greater than expected from placebo effects alone and persists for at least three months. Additional research is warranted to elucidate mechanistically how OMT exerts its effects, to determine if OMT benefits are long lasting, and to assess the cost-effectiveness of OMT as a complementary treatment for low back pain.
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Project description:Background: Minimal residual disease (MRD) has shown the prognostic value in mantle cell lymphoma (MCL). To quantify the relationships between progression free survival (PFS) and overall survival (OS) with MRD status in MCL, we conducted this meta-analysis. Methods: We searched databases including Pubmed, Embase, Web of Science and the Cochrane Library up to July 15th, 2020. Data of patients' characteristics, MRD assessment and survival outcomes were extracted and analyzed. Results: Ten articles were included. For the impact of post-induction MRD status on survival outcomes, MRD positive status was associated with worse PFS (HR=1.44; 95%CI 1.27-1.62; P<0.00001) and OS (HR=1.30; 95%CI 1.03-1.64; P=0.03) compared with MRD negative status. Regarding the impact of post-consolidation MRD status on survival outcomes, MRD positivity predicted shorter PFS (HR=1.84; 95%CI 1.49-2.26; P<0.00001) and OS (HR=2.38; 95%CI 1.85-3.06; P<0.00001) than MRD negativity. Conclusions: This study indicated that MRD positivity after induction and consolidation treatments was associated with worse PFS and OS for MCL. MRD-based treatment strategies should be further explored in clinical trials and real-world practice.
| S-EPMC7738989 | biostudies-literature
Project description:Mantle cell lymphoma (MCL) is an incurable rare subtype of non-Hodgkin lymphoma and is subject to relapse and therapeutic resistance. Molecular aberrations in MCL affect pathogenesis, prognosis, and therapeutic response. In this systematic review, we searched 3 databases and selected 32 articles that described mutations in MCL patients. We then conducted a meta-analysis using a Bayesian multiregression model to analyze patient-level data in 2127 MCL patients, including prevalence of mutations. In tumor or bone marrow samples taken at diagnosis or baseline, ATM was the most frequently mutated gene (43.5%) followed by TP53 (26.8%), CDKN2A (23.9%), and CCND1 (20.2%). Aberrations were also detected in IGH (38.4%) and MYC (20.8%), primarily through cytogenetic methods. Other common baseline mutations were NSD2 (15.0%), KMT2A (8.9%), S1PR1 (8.6%), and CARD11 (8.5%). Our data also show a change in mutational status from baseline samples to samples at disease progression and present mutations of interest in MCL that should be considered for future analysis. The genes with the highest mutational frequency difference (>5%) are TP53, ATM, KMT2A, MAP3K14, BTK, TRAF2, CHD2, TLR2, ARID2, RIMS2, NOTCH2, TET2, SPEN, NSD2, CARD11, CCND1, SP140, CDKN2A, and S1PR1. These findings provide a summary of the mutational landscape of MCL. The genes with the highest change in mutation frequency should be included in targeted next-generation sequencing panels for future studies. These findings also highlight the need for analysis of serial samples in MCL. Patient-level data of prevalent mutations in MCL provide additional evidence emphasizing molecular variability in advancing precision medicine initiatives in MCL.
| S-EPMC7362354 | biostudies-literature
Project description:Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto's method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs. chemotherapy alone; more extended vs. involved-field radiotherapy; radiation at higher doses vs. radiation at 20 Gy; more vs. fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs. intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival rates (P=0.007) as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (P=0.0028). No progression-free or overall survival differences were observed between combined-modality treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (P=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.
| S-EPMC5622859 | biostudies-other
Project description:Results of randomized controlled trials evaluating zinc for the treatment of the common cold are conflicting. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for such use.We searched electronic databases and other sources for studies published through to Sept. 30, 2011. We included all randomized controlled trials comparing orally administered zinc with placebo or no treatment. Assessment for study inclusion, data extraction and risk-of-bias analyses were performed in duplicate. We conducted meta-analyses using a random-effects model.We included 17 trials involving a total of 2121 participants. Compared with patients given placebo, those receiving zinc had a shorter duration of cold symptoms (mean difference -1.65 days, 95% confidence interval [CI] -2.50 to -0.81); however, heterogeneity was high (I(2) = 95%). Zinc shortened the duration of cold symptoms in adults (mean difference -2.63, 95% CI -3.69 to -1.58), but no significant effect was seen among children (mean difference -0.26, 95% CI -0.78 to 0.25). Heterogeneity remained high in all subgroup analyses, including by age, dose of ionized zinc and zinc formulation. The occurrence of any adverse event (risk ratio [RR] 1.24, 95% CI 1.05 to 1.46), bad taste (RR 1.65, 95% CI 1.27 to 2.16) and nausea (RR 1.64, 95% CI 1.19 to 2.27) were more common in the zinc group than in the placebo group.The results of our meta-analysis showed that oral zinc formulations may shorten the duration of symptoms of the common cold. However, large high-quality trials are needed before definitive recommendations for clinical practice can be made. Adverse effects were common and should be the point of future study, because a good safety and tolerance profile is essential when treating this generally mild illness.
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Project description:To perform a systematic review and network meta-analysis evaluating the efficacy and safety of low-molecular-weight heparins (LMWHs), vitamin K antagonists (VKAs), and direct-acting oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). We searched MEDLINE, Cochrane Central Register of Controlled Trials, and conference abstracts through March 2018. Randomized controlled trials (RCTs) enrolling adults with CAT comparing 2 or more full-dose anticoagulants (LMWH, VKA, and DOAC) and evaluating recurrent venous thromboembolism (VTE), major bleeding, and/or all-cause mortality were included. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. A frequentist network meta-analysis, which uses direct and indirect evidence to simultaneously compare multiple interventions, was performed using a random-effects approach. Results are reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). We included 13 RCTs (n = 6292): 7 compared LMWHs with VKAs, 4 compared DOACs with VKAs, and 2 compared DOACs with LMWHs. The risk of recurrent VTE was significantly reduced by 28% and 54% with a DOAC compared to an LMWH and a VKA, respectively. Low-molecular-weight heparins significantly reduced the risk of recurrent VTE by 36% versus VKAs. The risk of major bleeding was 14% higher with DOACs compared to LMWHs and 15% and 25% lower with DOACs and LMWHs versus VKAs, although 95% CIs included unity for each. The risk of all-cause mortality appeared similar for all 3 comparisons (RR = 1.0 for each comparison). Direct-acting oral anticoagulants appeared superior in reducing recurrent VTE in patients with CAT compared to LMWH and VKAs, but an increased risk of major bleeding versus LMWH cannot be ruled out.
| S-EPMC6714836 | biostudies-other
Project description:The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine (Hcy) with and without simultaneous supplementation of B-group vitamins or folic acid. A literature search was conducted in PubMed, EmBase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) reporting the concentration of serum Hcy in metformin-treated adults. Meta-analysis was applied to assess the association between metformin and the changes of Hcy concentration. Twelve publications were included in this study. In the overall analysis, metformin administration was not statistically associated with the change of Hcy when compared with the control treatment (mean difference (MD), 0.40 μmol/L; 95% confidence interval (CI), -0.07~0.87 μmol/L, p = 0.10). In the subgroup analysis, metformin was significantly associated with an increased concentration of Hcy in the absence of exogenous supplementation of folic acid or B-group vitamins (MD, 2.02 μmol/L; 95% CI, 1.37~2.67 μmol/L, p < 0.00001), but with a decreased concentration of serum Hcy in the presence of these exogenous supplementations (MD, -0.74 μmol/L; 95% CI, -1.19~-0.30 μmol/L, p = 0.001). Therefore, although the overall effect of metformin on the concentration of serum Hcy was neutral, our results suggested that metformin could increase the concentration of Hcy when exogenous B-group vitamins or folic acid supplementation was not given.
| S-EPMC5188453 | biostudies-literature
Project description:Background/objectiveThis systematic review aims to determine the potential effects of oral nutritional supplements (ONS) in patients receiving maintenance dialysis therapy (MDT).MethodsElectronic databases were searched without language limits through to July 2018. Randomized controlled trials (RCTs) that involved comparisons of ONS versus placebo or routine care are included in this meta-analysis. RevMan 5.3 statistical software was used for meta-analysis.Results15 articles with 589 subjects were included in our study. There are insufficient comparable data of randomized trials to allow meta-analysis of mortality. Albumin levels may be improved by the macronutrient blends or protein/amino acid supplements in MDT patients. Compared with the control group, serum albumin levels and BMI in the ONS group were increased by 1.58 g/L (95% CI, 0.52-2.63, P = 0.003; I2 = 85%) and 0.40 kg/m2 (95% CI, 0.10-0.71, P = 0.01; I2 = 49%), respectively. In the subgroup analysis of patients receiving hemodialysis, albumin levels in ONS group were increased by 2.17 g/L (95% CI, 0.89-3.45, P<0.001; I2 = 90%). ONS may not influence serum phosphorus and potassium levels.ConclusionsVery low-quality evidence suggests that Short-term oral energy or protein/amino acid supplements may improve nutritional status by increasing serum albumin levels and BMI in MDT patients, without influence on serum potassium levels. High-quality and large RCTs, particularly regarding the effects of ONS on mortality and quality of life, are needed to further validate our findings.
| S-EPMC6136747 | biostudies-literature
Project description:Some studies have indicated the efficacy of quetiapine in the treatment of generalized anxiety disorder (GAD).The purpose of this study was to systematically review the efficacy, acceptability, and tolerability of quetiapine in adult patients with GAD.The SCOPUS, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched in April 2015. All randomized controlled trials (RCTs) of GAD were considered to be included in this meta-analysis. All RCTs of quetiapine in GAD patients providing endpoint outcomes relevant to severity of anxiety, response rate, remission rate, overall discontinuation rate, or discontinuation rate due to adverse events were included. The version reports from suitable clinical studies were explored, and the important data were extracted. Measurement for efficacy outcomes consisted of the mean-changed scores of the rating scales for anxiety, and response rate.A total of 2,248 randomized participants in three RCTs were included. The pooled mean-changed score of the quetiapine-treated group was greater than that of the placebo-treated group and comparable to selective serotonin reuptake inhibitors (SSRIs). Unfortunately, the response and the remission rates in only 50 and 150 mg/day of quetiapine-XR (extended-release) were better than those of the placebo. Their response and remission rates were comparable to SSRIs. The rates of pooled overall discontinuation and discontinuation due to adverse events of quetiapine-XR were greater than placebo. Only the overall discontinuation rate of quetiapine-XR at 50 and 150 mg/day and the discontinuation rate due to adverse events of quetiapine-XR at 50 mg/day were comparable to SSRIs.Based on this meta-analysis, quetiapine-XR is efficacious in the treatment of GAD in adult patients. Despite its low acceptability and tolerability, the use of 50-150 mg/day quetiapine-XR for adult GAD patients may be considered as an alternative treatment. Further well-defined studies should be conducted to warrant these outcomes.
| S-EPMC4716733 | biostudies-other