scholarly journals The fragility index in 2010-2021 chronic lymphocytic leukemia randomized controlled trials

2021 ◽  
Author(s):  
Cristina Bagacean ◽  
Jean-Christophe Ianotto ◽  
Nanthara Sritharan ◽  
Florence Cymbalista ◽  
Christian Berthou ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Randomized Controlled Trials ◽  
Lymphocytic Leukemia ◽  
Controlled Trials ◽  
Fragility Index ◽  
Randomized Controlled

Ibrutinib for Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma: A Meta-Analysis of Randomized Controlled Trials

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5596-5596
Author(s):  
Shijia Zhang ◽  
Larysa Sanchez ◽  
Jieqi Liu ◽  
Victor Chang ◽  
Stuart L. Goldberg
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Controlled Trials ◽  
Small Lymphocytic Lymphoma ◽  
Bulky Disease ◽  
Free Survival ◽  
Randomized Controlled

Background: Ibrutinib, a Bruton's tyrosine kinase inhibitor, was approved by FDA for the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This study aims to evaluate the efficacy and safety data from randomized controlled trials (RCT) of ibrutinib-based therapy in patients with CLL or SLL. Methods: PubMed, ASH, and ASCO databases (2008-2016) were searched for randomized control trials of ibrutinib therapy (either single-agent or combination) for chronic lymphocytic leukemia or small lymphocytic lymphoma through June 30, 2016. Study endpoints included overall survival (OS), progression-free survival (PFS), and adverse events (AE). Pooled hazard ratios (HR) for survival outcomes and relative risks (RR) for dichotomous data with 95% confidence interval (CI) were calculated with a random effect model using MedCalc. Results: Four randomized controlled trials (RESONATE-1, RESONATE-2, HELIOS, and CLL12) were identified, but CLL12 trial was excluded from this study since the efficacy data were not available at the time of this meta-analysis. Pooled data from the 3 RCTs (1238 patients) showed that ibrutinib-based therapy improved overall survival (HR 0.419; 95% CI 0.242-0.725, P = 0.002) and progression-free survival (HR 0.201; 95% CI 0.162-0.251, P < 0.001) compared to regimens without ibrutinib. Subgroup analysis showed that the PFS benefits were independent of sex (male: HR 0.188, 95% CI 0.143-0.249, P < 0.001; female: HR 0.225, 95% CI 0.154-0.331, P < 0.001), Rai stage (0-II: HR 0.154, 95% CI 0.109-0.217, P < 0.001; III-IV: HR 0.235, 95% CI 0.167-0.333, P < 0.001), bulky disease (<5 cm: HR 0.219, 95% CI 0.155-0.309, P < 0.001; ≥5 cm: HR 0.179, 95% CI 0.135-0.238, P < 0.001) or chromosome 11q deletion (positive: HR 0.099, 95% CI 0.060-0.163, P < 0.001; negative: HR 0.261, 95% CI 0.212-0.322, P < 0.001). Ibrutinib-based therapy significantly increased the risk of developing all-grade diarrhea (RR = 2.135, 95% CI = 1.437-3.174, p < 0.001), pyrexia (RR = 1.265, 95% CI = 1.011-1.583, p = 0.040), and arthralgia (RR = 1.863, 95% CI = 1.101-3.152, p = 0.020), but not anemia (RR = 0.955, 95% CI = 0.694-1.313, p = 0.777), neutropenia (RR = 1.048, 95% CI = 0.760-1.446, p = 0.774), fatigue (RR = 0.897, 95% CI = 0.746-1.078, p = 0.247), or nausea (RR = 0.951, 95% CI = 0.600-1.506, p = 0.829). Conclusions: Ibrutinib-based therapy significantly improves OS and PFS (independent of sex, Rai stage, bulky disease or chromosome 11q deletion) in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, but increases the risks of all-grade adverse events including diarrhea, pyrexia, and arthralgia. Disclosures Chang: Johnson and Johnson: Other: Stock; Amgen: Other: Research; Boehringer Ingelheim: Other: Research. Goldberg:Neostem: Equity Ownership; Bristol Myers Squibb, Novartis: Speakers Bureau; COTA Inc: Employment; Pfizer: Honoraria; Novartis: Consultancy.

Forest Plot to Compare Therapies in a Network Meta-Analysis in First Line Chronic Lymphocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4596-4596
Author(s):  
Alfonso Piciocchi ◽  
Katia Bontempi ◽  
Paola Fazi ◽  
Marco Vignetti ◽  
Franco Mandelli
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Randomized Controlled Trials ◽  
Disease Progression ◽  
Meta Analysis ◽  
Lymphocytic Leukemia ◽  
Forest Plot ◽  
Controlled Trials ◽  
First Line ◽  
Early Stage Disease ◽  
Randomized Controlled

Abstract Abstract 4596 Several therapies, composed by single agent or combinations, are available for untreated patients in chronic lymphocytic leukemia and it is difficult to rank treatments according to their effect size when not all treatments have been compared directly. Direct randomized comparison is the most reliable way of comparing treatments but when the number of available treatments increases the number of possible pairwise comparisons increases quadratically, so it is common for only a small fraction of the possible comparisons to be performed. Network meta-analysis permits to add indirect estimates for assessing the relative effectiveness of two treatments when they have not been compared directly in a randomized trial but have each been compared to other treatments. Network meta-analysis of randomized controlled trials was used to combine direct and indirect estimates of the effect of four drugs and their combinations from five randomized controlled trials (Fig. IA) in CLL patients based on a systematic review conducted by M.M. Cheng et al. (Cancer Treatment Review 2012) on 2625 patients where Chorambucil, Fludarabine, Rituximab, Alemtuzumab, Bendamustine, Cladribine and Pentostatin have been considered as primary first-line agents for CLL. Patients were younger (59–65 years), had good performance status (ECOG: 0–1) and early stage disease (Rai 0-II, Binet A or B). We carried out an analysis based on the endpoint of PFS, described as the duration of the time from randomization until disease progression or death from any cause and to consider the heterogeneity among the studies a random effects model was performed. The differences in PFS of all therapies considered in the analysis were compared with combination of Fludarabine and Chorambucil (FC). The results were summarized by forest plot (Fig IB) in terms of reduction or increase of Hazard Ratio. As the forest plot shows, FCR has relatively higher potential of preventing disease progression in younger patients affected by chronic lymphocytic leukemia. Respect to a traditional meta-analysis, which usually compares only two treatments, network meta-analysis is a useful method to combine direct and indirect comparisons of treatments from RCTs and to analyze the hierarchy in treatment effects and tests for consistency of the relations of the network. Disclosures: No relevant conflicts of interest to declare.

The Fragility Index in Hand Surgery Randomized Controlled Trials

2019 ◽  
Vol 44 (8) ◽  
pp. 698.e1-698.e7 ◽  
Author(s):  
Joseph J. Ruzbarsky ◽  
Sariah Khormaee ◽  
Aaron Daluiski
Keyword(s):  
Randomized Controlled Trials ◽  
Hand Surgery ◽  
Controlled Trials ◽  
Fragility Index ◽  
Randomized Controlled

scholarly journals The Fragility Index in a Cohort of Pediatric Randomized Controlled Trials

2017 ◽  
Vol 6 (8) ◽  
pp. 79 ◽  
Author(s):  
Travis Matics ◽  
Nadia Khan ◽  
Priti Jani ◽  
Jason Kane
Keyword(s):  
Randomized Controlled Trials ◽  
Controlled Trials ◽  
Fragility Index ◽  
Randomized Controlled

scholarly journals Efficacy of Cancer Immunotherapy: An Umbrella Review of Meta-analyses of Randomized Controlled Trials

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1801 ◽  
Author(s):  
Kim ◽  
Lee ◽  
Eisenhut ◽  
Vliet ◽  
Kronbichler ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Cancer Immunotherapy ◽  
Prediction Interval ◽  
Convincing Evidence ◽  
Lymphocytic Leukemia ◽  
Interferon Α ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Meta Analyses ◽  
Cancer Immunotherapies

We conducted a systematic review for evidence of the clinical efficacy of cancer immunotherapies. We searched PubMed from inception to 14 February 2018 for meta-analyses of randomized controlled trials (RCTs) of cancer immunotherapies. Re-analyses were performed to estimate the summary effect size under random-effects, the 95% confidence interval (CI), heterogeneity, and the 95% prediction interval, and we determined the strength of the evidence. We examined publication bias and excess significance bias. 63 articles corresponding to 247 meta-analyses were eligible. Nine meta-analyses were classified to have convincing evidence, and 75 were classified as suggestive evidence. The clinical benefit of immunotherapy was supported by convincing evidence in the following settings: anti-PD-1/PD-L1 monoclonal antibody (mAb) therapy for treating advanced melanoma and non-small cell lung cancer (NSCLC), the combination of rituximab and chemotherapy for treating chronic lymphocytic leukemia and B-cell non-Hodgkin’s lymphoma, adoptive cell immunotherapy for NSCLC, and the combination of interferon α and chemotherapy for metastatic melanoma. A further meta-analysis of 16 RCTs showed that anti-PD-1/PD-L1 mAb therapy had a benefit in patients with solid tumors (overall survival; hazard ratio = 0.73, 95% CI: 0.68–0.79; p < 0.001), supported by convincing evidence. In the future, rigorous approaches are needed when interpreting meta-analyses to gain better insight into the true efficacy of cancer immunotherapy.

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