scholarly journals Efficacy of rituximab maintenance therapy for aggressive B-cell lymphoma depends on use of rituximab in induction therapy: a meta-analysis of randomized controlled trials

Haematologica ◽  
2015 ◽  
Vol 100 (12) ◽  
pp. e519-e520 ◽  
Author(s):  
Y. Nannya ◽  
N. Goto ◽  
M. Shimizu ◽  
M. Seishima ◽  
H. Tsurumi
Keyword(s):  
Maintenance Therapy ◽  
Randomized Controlled Trials ◽  
B Cell ◽  
Induction Therapy ◽  
Cell Lymphoma ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Aggressive B Cell Lymphoma

scholarly journals Bortezomib-Based Consolidation/Maintenance Therapy for Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3293-3293
Author(s):  
Shijia Zhang ◽  
Yucai Wang ◽  
Yvonne Datta ◽  
Veronika Bachanova ◽  
Sarah Cooley
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Randomized Controlled Trials ◽  
Induction Therapy ◽  
Meta Analysis ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Grade 3

Abstract Background: Bortezomib is a proteasome inhibitor that can lead to cell-cycle arrest and apoptosis. Bortezomib-based regimens are widely used as induction therapy of multiple myeloma (MM). Unlike lenalidomide (an immunomodulatory drug), the role of bortezomib in the consolidation and maintenance therapy of multiple myeloma is less clear. This study aims to examine the efficacy and safety of bortezomib-based regimens as consolidation/maintenance therapy in MM patients following induction therapy with or without autologous stem cell transplantation (ASCT). Methods: PubMed, ASH, and ASCO databases were searched for randomized controlled trials (RTC) of bortezomib-based regimens (either single-agent or combination) as consolidation/maintenance therapy for MM patients through July 2018. 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 (MedCalc Software, Ostend, Belgium). For studies that did not report HRs for survival outcomes but provided graphical survival curves, the log HRs and variances were estimated based on the method by Parmar et al (Stat Med 1998; 17: 2815-2834). Heterogeneity was assessed using the I2 statistic of inconsistency, with statistically significant heterogeneity defined as I2 > 50% or p-value < 0.1. Results: Eight randomized controlled trials (7 phase III, 1 phase II; 2 were published in a single article) were identified. Bortezomib-based regimens were administered as consolidation treatment in 5 RTCs and maintenance therapy in 3 RTCs, following induction therapy +/- ASCT. A total of 2439 patients were included: 1154 patients received bortezomib-based regimens, and 1285 patients received non-bortezomib-based regimens or observation. Two RCTs (1 for consolidation, 1 for maintenance) did not provide HRs, which were estimated as described as above. Pooled data from the 8 RCTs showed that bortezomib-based consolidation/maintenance therapy improved progression-free survival (HR 0.71, 95% CI 0.64-0.79, P < 0.001; I2 = 6.61%) and overall survival (HR 0.80, 95% CI 0.68-0.94, P = 0.005; I2 = 0%) compared to observation or regimens without bortezomib. When the 2 RCTs that did not report HRs were excluded from the meta-analysis, it did not alter the favorable outcome of bortezomib-based consolidation/maintenance therapy: PFS (HR 0.70, 95% CI 0.60-0.82, P < 0.001; I2 = 40.54%) and OS (HR 0.76, 95% CI 0.64-0.91, P = 0.002; I2 = 0%). The PFS benefit was maintained in a subgroup analysis by the setting of treatment (consolidation, HR 0.73, 95% CI 0.63-0.85, P < 0.001; I2 = 0%, maintenance, HR 0.70, 95% CI 0.56-0.0.86, P = 0.001; I2 = 55.63%). Bortezomib-based therapy prolonged OS in the maintenance setting (HR 0.71, 95% CI 0.58-0.86, P < 0.001; I2 = 0%) but not in the consolidation setting (HR 1.01, 95% CI 0.77-1.33, P = 0.935; I2 = 0%). Regarding safety, bortezomib-based consolidation/maintenance therapy significantly increased the risk of grade 3 or 4 peripheral sensory neuropathy and neuralgia (RR 2.09, 95% CI 1.11-3.95, p = 0.022; I2 = 52.64%) compared to observation or regimens without bortezomib. There was a trend toward increased rates of grade 3 or 4 thrombocytopenia (RR 1.54, 95% CI 0.95-2.52, p = 0.08; I2 = 21.67%), GI symptoms (RR 2.54, 95% CI 0.63-10.25, p = 0.19; I2 = 76.72%), vascular events (RR 1.90, 95% CI 0.80-4.53, p = 0.15; I2 = 0.00%), and fatigue (RR 2.10, 95% CI 0.83-5.30, p = 0.12; I2 = 0.00%) with bortezomib-based consolidation/maintenance, but these did not reach statistical significance. Conclusions: Bortezomib-based consolidation/maintenance significantly improves PFS and OS in MM patients following induction therapy +/- ASCT. The OS benefit appears to be limited to the maintenance setting based on a subgroup analysis. Bortezomib-based regimen increases the risk of grade 3 or 4 peripheral sensory neuropathy and neuralgia. Disclosures Bachanova: Gamida Cell: Research Funding; GT Biopharma: Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees.

Maintenance Therapies for Multiple Myeloma (MM): A Network Meta-Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 236-236
Author(s):  
Helen Mahony ◽  
Ambuj Kumar ◽  
Rahul Mhaskar ◽  
Branko Miladinovic ◽  
Keith Wheatley ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Phase Iii ◽  
Novel Agents ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomized Controlled ◽  
American Society ◽  
Novel Agent

Abstract Abstract 236 Background: There is little consensus on which maintenance therapy clinicians should choose for their patients. Since 1999, the three novel agents of bortezomib, lenalidomide, and thalidomide have been approved for use among patients with MM. These agents have been increasingly used as maintenance therapy. To date, only two randomized controlled trials of maintenance therapy have examined the efficacy of these novel agents head-to-head. Here, we conduct a network meta-analysis of bortezomib, lenalidomide, and thalidomide to determine which of these novel agents could potentially increase overall survival (OS) and progression-free survival (PFS). Methods: A comprehensive literature search of MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and meetings abstracts from American Society of Hematology, American Society of Clinical Oncology, European Society for Medical Oncology and European Hematology Association was undertaken to identify all phase III randomized controlled trials (RCTs) of maintenance therapy published until July 2012. We applied the Bayesian mixed treatment comparison (MTC) method under the random-effects model. The indirect comparisons were constructed from trials that have one treatment in common. For each included RCT, we calculated the hazard ratio (HR) and its corresponding standard error and used this to calculate the indirect estimates of HR and corresponding credible intervals (CrI). We also ranked the treatments according to the probability of best treatment and calculated the surface underneath the cumulative ranking curve (SUCRA). All analyses were conducted in WinBUGS 1.4.3 and Stata 11.2. Results: The network, number of trials for each comparison, and number of patients enrolled is shown in Figure 1. The network for OS was based on 12 RCTs enrolling 5542 patients and the network for PFS was constructed from 13 RCTs and 5784 patients. The MTC networks were consistent for both OS and PFS. For both OS and PFS, two comparisons were produced (Figure 2). For OS, the analysis showed that none of the treatments were superior. For PFS, lenalidomide was superior to thalidomide (HR = 0.58, 95% CrI [0.37, 0.94]). The estimates of SUCRA and rank probabilities (Figure 3) suggested that for OS bortezomib was best followed by lenalidomide and thalidomide. For PFS, lenalidomide was best followed by bortezomib and thalidomide. Conclusion: Using the MTC method, we found no evidence that any of the novel agents are superior to one another in terms of OS. Lenalidomide was the only novel agent which was superior to another active therapy (thalidomide). While these results provide preliminary evidence to which novel agent may be more beneficial as maintenance therapy, definitive conclusions cannot be reached until large, well designed RCTs evaluating these therapies head-to-head are conducted. Disclosures: No relevant conflicts of interest to declare.

A systematic review and meta-analysis of randomized controlled trials to evaluate the risk of fatigue and pain among patients treated with ibrutinib.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 213-213
Author(s):  
Myo Zaw ◽  
Kyaw Zin Thein ◽  
Myat M. Han ◽  
Ruth D’Cunha ◽  
Hassan Kaleem ◽  
...  
Keyword(s):  
Systematic Review ◽  
Back Pain ◽  
Side Effects ◽  
Randomized Controlled Trials ◽  
B Cell ◽  
Meta Analysis ◽  
Cell Receptor ◽  
Muscle Spasm ◽  
Controlled Trials ◽  
Randomized Controlled

213 Background: Bruton’s tyrosine kinase (BTK), a kinase downstream of the B-cell receptor, involves in the B cell survival and proliferation and has become an attractive therapeutic target. Ibrutinib is an oral potent, covalent inhibitor of BTK and hence employed in many hematologic malignancies. We performed a systematic review and pooled analysis of randomized controlled trials (RCTs) to determine the risk of fatigue and pain among patients treated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts through December 31, 2016. RCTs that mention fatigue, arthralgia, muscle spasm, back pain, pain in extremity and myalgia as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: Four phase 3 RCTs with a total of 1505 patients were eligible for the analysis. Studies compared Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B)+ rituximab (R) vs placebo + B+ R and I vs temsirolimus were included in the analysis. The relative risks (RR) of all-grade side effects were as follows: fatigue, 0.87 (95% CI: 0.74- 1.03, p = 0.11); arthralgia, 1.97 (95% CI: 1.11- 3.50, p = 0.02); muscle spasm, 1.92 (95% CI: 1.22- 3.02, p = 0.005); back pain, 1.56 (95% CI: 1.02- 2.37, p = 0.03); pain in extremity, 2.47 (95% CI: 1.14- 5.36, p = 0.02); and myalgia, 2.68 (95% CI: 1.18- 6.05, p = 0.01). The RR of high-grade side effects were as follows: fatigue, 0.70 (95% CI: 0.37- 1.33, p = 0.28); arthralgia, 3.62 (95% CI: 0.74- 17.66, p = 0.11); back pain, 2.80 (95% CI: 0.42- 18.35, p = 0.28); pain in extremity, 2.96 (95% CI: 0.31- 28.4, p = 0.34); and myalgia, 2.96 (95% CI: 0.31- 28.44, p = 0.34). Conclusions: Our meta-analysis demonstrated that the risk of all-grade arthralgia, muscle spasm, back pain, pain in extremity and myalgia with ibrutinib was high. Pain is a major determinant of quality of life in cancer patients undergoing chemotherapy and recognizing these may help clinicians in delivering proper supportive care.

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