scholarly journals Immunomodulatory drug and dexamethasone-containing triple versus doublet combination treatments for relapsed or refractory multiple myeloma: a meta-analysis of phase III randomized controlled trials

2020 ◽  
Author(s):  
Minjie Gao ◽  
Xiao Yan ◽  
Fei Li ◽  
Kaihong Xu ◽  
Qitian Mu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Phase Iii ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Refractory Multiple Myeloma ◽  
Randomized Controlled ◽  
Immunomodulatory Drug ◽  
Grade 3

Abstract Background Triplet therapy has become the standard of care for relapsed or refractory multiple myeloma (RRMM) over the past few years. Prior to that, doublet therapy including dexamethasone and an immunomodulatory were standard. Several systematic studies have been conducted and many combinations with variable triplet therapies but have not always used the former standard therapy as a benchmark. The objective of this meta-analysis was to evaluate the efficacy and safety of triplet combinations that included dexamethasone and an immunomodulatory drug versus a doublet combination of just dexamethasone and an immunomodulatory for the treatment of RRMM. Methods A comprehensive literature search (PubMed, EMBASE, Cochrane Library) for phase III randomized controlled trials for efficacy and safety of triplet versus doublet combinations that specifically included dexamethasone and an immunomodulatory drug for treatment of RRMM. Efficacy (ORR, PFS, OS) and adverse events (≥ grade 3) were assessed using traditional statistical measures for aggregate data. Results Of 235 potential reports, 6 met the inclusion criteria (N = 115–792 participants). The methodological quality was ≥ 4 Jadad score for each. Triplet treatment had higher ORR (HR = 0.74, 95%CI: 0.65–0.84, P ≤ 0.001), PFS (HR = 0.63, 95%CI: 0.52–0.75, P ≤ 0.001), and OS (HR = 0.74, 95%CI: 0.65–0.84, P ≤ 0.001). The incidence of ≥ grade 3 diarrhea and fatigue were significantly higher in the triplet combination group. There was a trend toward increased incidence of ≥ grade 3 neutropenia, thrombocytopenia, thromboembolism, and peripheral neuropathy in the triplet therapy group. Notably, triplet therapy had a significantly lower rate of anemia compared to doublet therapy. Conclusions This study reinforces current guidelines and recommendations for triplet combinations containing dexamethasone and an immunomodulatory drug.

Comparison of Monoclonal Antibodies targeting CD38, SLAMF7 and PD-1/PD-L1 in combination with Bortezomib/Immunomodulators plus Dexamethasone/Prednisone for the treatment of Multiple Myeloma: An Indirect-Comparison Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
Wu Ye ◽  
Xia Wu ◽  
Xiaoyan Liu ◽  
Xue Zheng ◽  
Jili Deng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Partial Response ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Group Versus ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Grade 3

Abstract Background In recent years, there were many clinical trials assessed the efficacy and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisoneare for the treatment of multiple myeloma (MM). The treatment outcomes of comparing different MAbs in combination with above-mentioned agents remain unknown. We conducted this meta-analysis to compare indirectly the efficacy and safety of MAbs targeting CD38, SLAMF7 and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/ prednisone in patients with MM. Methods We electronically searched for randomized controlled trials (RCTs) in which at least one of the three MAbs was included among multiple arms. We included eleven eligible RCTs with 5367 patients in the meta-analysis. Statistical analysis used StataMP14 and Indirect Treatment Comparisons software. Results We synthesized hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), relative risk (RR) for overall response rate, complete response (CR) or better, very good partial response (VGPR) or better, VGPR, partial response, stable disease and grade 3 or higher adverse events among the three groups. The HR for PFS of the CD38 group vs SLAMF7 group, CD38 group vs PD-1/PD-L1 group and SLAMF7 group vs PD-1/PD-L1 group were 0.662(95CI0.543-0.806), 0.317(95CI 0.221–0.454) and 0.479(95CI0.328-0.699) respectively. The HR for OS of the CD38 group vs SLAMF7 group was 0.812(0.584–1.127). The RR for CR or better in the CD38 group versus SLAMF7 group was 2.253(95CI1.284-3.955). The RR for neutropenia of the CD38 group versus SLAMF7 group was 1.818(95CI1.41-2.344). Conclusions Treatment with the CD38 group resulted in longer PFS and better treatment response than the SLAMF7 and PD-1/PD-L1 group. In addition, the SLAMF7 group prolonged PFS compared with the PD-1/PD-L1 group, and had a lower incidence of grade 3 or higher neutropenia than the CD38 and PD-1/PD-L1 group. In

scholarly journals Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 358
Author(s):  
Claudio Ricci ◽  
Giuseppe Lamberti ◽  
Carlo Ingaldi ◽  
Cristina Mosconi ◽  
Nico Pagano ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Neuroendocrine Neoplasms ◽  
Controlled Trials ◽  
Endocrine Tumors ◽  
Randomized Controlled ◽  
Grade 3

Several new therapies have been approved to treat advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP–NENs) in the last twenty years. In this systematic review and meta-analysis, we searched MEDLINE, ISI Web of Science, and Scopus phase III randomized controlled trials (RCTs) comparing two or more therapies for unresectable GEP–NENs. Network metanalysis was used to overcome the multiarm problem. For each arm, we described the surface under the cumulative ranking (SUCRA) curves. The primary endpoints were progression-free survival and grade 3–4 of toxicity. We included nine studies involving a total of 2362 patients and 5 intervention arms: SSA alone, two IFN-α plus SSA, two Everolimus alone, one Everolimus plus SSA, one Sunitinib alone, one 177Lu-Dotatate plus SSA, and one Bevacizumab plus SSA. 177Lu-Dotatate plus SSA had the highest probability (99.6%) of being associated with the longest PFS. This approach was followed by Sunitinib use (64.5%), IFN-α plus SSA one (53.0%), SSA alone (46.6%), Bevacizumab plus SSA one (45.0%), and Everolimus ± SSA one (33.6%). The placebo administration had the lowest probability of being associated with the longest PFS (7.6%). Placebo or Bevacizumab use had the highest probability of being the safest (73.7% and 76.7%), followed by SSA alone (65.0%), IFN-α plus SSA (52.4%), 177Lu-Dotatate plus SSA (49.4%), and Sunitinib alone (28.8%). The Everolimus-based approach had the lowest probability of being the safest (3.9%). The best approaches were SSA alone or combined with 177Lu-Dotatate.

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.

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