The magnitude of improvement in progression-free survival with targeted therapy in relapsed/refractory chronic lymphocytic leukemia based on prognostic risk category: a systematic review and meta-analysis

2018 ◽  
Vol 60 (7) ◽  
pp. 1644-1649 ◽  
Author(s):  
Stefano Molica ◽  
Diana Giannarelli ◽  
Rosanna Mirabelli ◽  
Luciano Levato ◽  
Tait D. Shanafelt
Keyword(s):  
Systematic Review ◽  
Targeted Therapy ◽  
Chronic Lymphocytic Leukemia ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Risk Category ◽  
Free Survival

scholarly journals FCR achieves long-term durable remissions in patients with IGHV-mutated CLL

Blood ◽  
2017 ◽  
Vol 130 (21) ◽  
pp. 2278-2282 ◽  
Author(s):  
Chatree Chai-Adisaksopha ◽  
Jennifer R. Brown
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Complete Remission ◽  
Randomized Trials ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Inclusion Criteria ◽  
Free Survival

Abstract In chronic lymphocytic leukemia (CLL) patients with mutated IGHV, 3 recent studies have demonstrated prolonged progression-free survival (PFS) after treatment with fludarabine-cyclophosphamide-rituximab (FCR) chemoimmunotherapy. We performed a systematic review to assess the benefit of FCR for patients with CLL and identified 5 randomized trials that met our inclusion criteria. FCR improved complete remission, PFS and overall survival vs the comparator; median PFS was not reached in the subgroup of CLL patients with mutated IGHV.

scholarly journals Treatment Outcomes of Novel Targeted Agents in Relapse/Refractory Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-Analysis

2019 ◽  
Vol 8 (5) ◽  
pp. 737 ◽  
Author(s):  
Po-Huang Chen ◽  
Ching-Liang Ho ◽  
Chin Lin ◽  
Yi-Ying Wu ◽  
Tzu-Chuan Huang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Targeted Agents ◽  
Free Survival ◽  
Risk Of Progression

Most chronic lymphocytic leukemia patients experience a relapse or become refractory to treatment with conventional chemotherapeutic agents. The network meta-analysis assesses the relative efficacy of novel targeted agents for the treatment of a relapse or refractory chronic lymphocytic leukemia. A systematic literature search included seven phase III randomized controlled trials, including a total of 2512 patients treated with nine regimens. Data were extracted and evidence synthesized using network meta-analysis. All novel targeted therapies were significantly more effective than ofatumumab and demonstrated promising prolongation of progression free survival (PFS), with a hazard ratio (HR) ranging from 0.10 to 0.52. Two novel targeted agent regimens, venetoclax plus rituximab and ibrutinib monotherapy, resulted in greater overall survival (HR, 0.335 and 0.361, respectively). Venetoclax plus rituximab and ibrutinib monotherapy were most favorable based on (1) HR for PFS compared with ofatumumab (Ibrutinib: HR, 0.10; 95% CI, 0.07–0.14; Venetoclax plus rituximab: HR, 0.10; 95% CI, 0.05–0.21) and SUCRA value (probability of being best) (Ibrutinib SUCRA, 0.92; Venetoclax rituximab SUCRA, 0.90) (2) HR for overall survival compared with ofatumumab (Ibrutinib: HR, 0.361; 95% CI, 0.208–0.627; Venetoclax rituximab: HR, 0.335; 95% CI, 0.112–0.997) and SUCRA value (Ibrutinib SUCRA, 0.84; Venetoclax rituximab SUCRA, 0.85) Both treatments reduced the risk of progression or death by 90% versus conventional ofatumumab. Both ibrutinib monotherapy and venetoclax rituximab have a high probability of being the most effective treatments for a relapse or refractory chronic lymphocytic leukemia with respect to long-term progression-free survival and overall survival.

Rituximab for Patients with Chronic Lymphocytic Leukemia: A Systematic Review

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4632-4632
Author(s):  
Kathrin Bauer ◽  
Olaf Weingart ◽  
Ina Monsef ◽  
Skoetz Nicole ◽  
Thomas Elter ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Chronic Lymphocytic Leukemia ◽  
Treatment Option ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Relative Effect ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Effective Treatment Option

Abstract Abstract 4632 Introduction: Chronic lymphocytic leukemia (CLL) accounts for 25% of all leukemias and remains incurable with conventional chemotherapy (CX). Rituximab (R) may be an effective treatment option for CLL patients with the potential to improve overall survival (OS) when given in combination with CX but there is also a risk of more side effects such as infections. This review aims to summarize the evidence for this new treatment option by evaluating the effects on OS, progression-free survival (PFS) and side effects. Methods: MEDLINE and CENTRAL were systematically searched for randomized controlled trials up to April 2010. Trials of patients with CLL comparing CX including R and treatment with CX alone (CX identical in both groups) were included. Clinical trials with previously untreated and pre-treated patients were explored in the main meta-analyses. Trial selection, quality assessment and data extraction were done independently by two review authors. Dichotomous data were analyzed as relative effect measures (i.e. relative risk, RR) with 95% confidence intervals (CI). Time-to-event outcomes were analyzed with hazard ratios (HR) and 95% CI in a random effects model. Results: A total of 992 records were screened. Two eligible trials with 921 untreated (GCLLSG CLL 8 trial (CLL8) and CALGB 9712 trial (CALGB 9712)) and two eligible trials with 604 pre-treated patients (REACH trial (REACH) and NCRI CLL 201 trial) that were fitting the inclusion criteria were identified. The NCLRI CLL 201 trial provided response data only. CALGB 9721 did not report HRs or P-values on OS or PFS and the survival curves for PFS and OS were of low quality, so the provided data were not included in the meta-analysis. Both, CLL8 and REACH examined patients receiving fludarabine (F) and cyclophosphamide (C) with or without R and were meta-analyzed with regard to PFS and OS. PFS (1342 patients) was significantly longer for FCR (HR 0.65, 95% CI [0.48, 0.88]). Analysis of OS (1368 patients) also showed a significantly longer survival for FCR (HR 0.73 (95% CI [0.58, 0.93]). CLL8 provided HRs for the different disease stages and showed significantly improved OS after FCR for Binet B patients only [Binet A: HR 0,19, 95% CI [0.23, 1.613]; Binet B: HR 0.45, 95% CI [0.295, 0.689]; Binet C: HR 1.4, 95% CI [0.843, 2.620]). REACH had not been significant regarding OS (HR 0.83, 95% CI [0.59, 1.17]). With regard to severe hematologic toxicity, meta-analysis of CLL8, REACH and CALGB 9721 showed a significantly higher risk of neutropenia (RR 1.46, CI 95% [1.03, 2.08]) for regimens including R, but there was no statistical difference for thrombocytopenia (RR 1.06, CI 95% [0.60, 1.87]), anemia (RR 0.89 [0.63, 1.26]) or the incidence of severe infections (RR 1.08 CI 95% [0.86, 1.35]). REACH reported a higher rate of secondary malignancies in the FCR-arm (FCR (7%), FC (5%)). Conclusions: This systematic review demonstrates significantly longer OS for CLL patients that received FCR compared to FC (HR 0.65, 95% CI [0.48, 0.88]) and confirms better PFS for patients receiving FCR (HR 0.73 (95% CI [0.58, 0.93]). Adverse events (particularly neutropenia) occurred more often when patients were treated with CX plus R but did not result in an increased infection rate. However, data of CLL8 were only available from the abstract and need to be subsequently confirmed. Disclosures: Hallek: Roche: Consultancy, Honoraria, Research Funding.

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.

scholarly journals Management of low-grade glioma: a systematic review and meta-analysis

2018 ◽  
Vol 6 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Timothy J Brown ◽  
Daniela A Bota ◽  
Martin J van Den Bent ◽  
Paul D Brown ◽  
Elizabeth Maher ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Low Grade Glioma ◽  
World Health ◽  
Subtotal Resection ◽  
Low Grade ◽  
Evidence Based ◽  
Free Survival ◽  
Low Grade Gliomas

Abstract Background Optimum management of low-grade gliomas remains controversial, and widespread practice variation exists. This evidence-based meta-analysis evaluates the association of extent of resection, radiation, and chemotherapy with mortality and progression-free survival at 2, 5, and 10 years in patients with low-grade glioma. Methods A quantitative systematic review was performed. Inclusion criteria included controlled trials of newly diagnosed low-grade (World Health Organization Grades I and II) gliomas in adults. Eligible studies were identified, assigned a level of evidence for every endpoint considered, and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relative risk of mortality and of progression at 2, 5, and 10 years was calculated for patients undergoing resection (gross total, subtotal, or biopsy), radiation, or chemotherapy. Results Gross total resection was significantly associated with decreased mortality and likelihood of progression at all time points compared to subtotal resection. Early radiation was not associated with decreased mortality; however, progression-free survival was better at 5 years compared to patients receiving delayed or no radiation. Chemotherapy was associated with decreased mortality at 5 and 10 years in the high-quality literature. Progression-free survival was better at 5 and 10 years compared to patients who did not receive chemotherapy. In patients with isocitrate dehydrogenase 1 gene (IDH1) R132H mutations receiving chemotherapy, progression-free survival was better at 2 and 5 years than in patients with IDH1 wild-type gliomas. Conclusions Results from this review, the first to quantify differences in outcome associated with surgery, radiation, and chemotherapy in patients with low-grade gliomas, can be used to inform evidence-based management and future clinical trials.

scholarly journals Relationship between Progression-Free Survival and Overall Survival in Chronic Lymphocytic Leukemia

2012 ◽  
Vol 23 ◽  
pp. ix350
Author(s):  
C. Beauchemin ◽  
J.B. Johnston ◽  
M. Lapierre ◽  
F. Aissa ◽  
J. Lachaine
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival

Therapeutic efficacy of specific immunotherapy for glioma: a systematic review and meta-analysis

2018 ◽  
Vol 29 (4) ◽  
pp. 443-461 ◽  
Author(s):  
Sara Hanaei ◽  
Khashayar Afshari ◽  
Armin Hirbod-Mobarakeh ◽  
Bahram Mohajer ◽  
Delara Amir Dastmalchi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Clinical Trials ◽  
Specific Immunotherapy ◽  
Data Extraction ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Control Group ◽  
Free Survival ◽  
Median Difference

Abstract Although different immunotherapeutic approaches have been developed for the treatment of glioma, there is a discrepancy between clinical trials limiting their approval as common treatment. So, the current systematic review and meta-analysis were conducted to assess survival and clinical response of specific immunotherapy in patients with glioma. Generally, seven databases were searched to find eligible studies. Controlled clinical trials investigating the efficacy of specific immunotherapy in glioma were found eligible. After data extraction and risk of bias assessment, the data were analyzed based on the level of heterogeneity. Overall, 25 articles with 2964 patients were included. Generally, mean overall survival did not statistically improve in immunotherapy [median difference=1.51; 95% confidence interval (CI)=−0.16–3.17; p=0.08]; however, it was 11.16 months higher in passive immunotherapy (95% CI=5.69–16.64; p<0.0001). One-year overall survival was significantly higher in immunotherapy groups [hazard ratio (HR)=0.69; 95% CI=0.52–0.92; p=0.01]. As the hazard rate in the immunotherapy approach was 0.83 of the control group, 2-year overall survival was significantly higher in immunotherapy (HR=0.83; 95% CI=0.69–0.99; p=0.04). Three-year overall survival was significantly higher in immunotherapy as well (HR=0.67; 95% CI=0.48–0.92; p=0.01). Overall, median progression-free survival was significantly higher in immunotherapy (standard median difference=0.323; 95% CI=0.110–0.536; p=0.003). However, 1-year progression-free survival was not remarkably different between immunotherapy and control groups (HR=0.94; 95% CI=0.74–1.18; p=0.59). Specific immunotherapy demonstrated remarkable improvement in survival of patients with glioma and could be a considerable choice of treatment in the future. Despite the current promising results, further high-quality randomized controlled trials are required to approve immunotherapeutic approaches as the standard of care and the front-line treatment for glioma.

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