Bortezomib in combination with thalidomide or lenalidomide or doxorubicin regimens for the treatment of multiple myeloma: a meta-analysis of 14 randomized controlled trials

2014 ◽  
Vol 55 (7) ◽  
pp. 1479-1488 ◽  
Author(s):  
Long Wang ◽  
Yan-Li Xu ◽  
Xiu-Qun Zhang
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled

Thromboprophylaxis In Multiple Myeloma Patients Undergoing Immunomodulatory Therapy with Thalidomide and Lenalidomide: A Systematic Review and Meta-Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1090-1090
Author(s):  
Marc Carrier ◽  
Gregoire Le Gal ◽  
Jason Tay ◽  
Cynthia M. Wu ◽  
Agnes Y. Lee
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Newly Diagnosed ◽  
Bleeding Events ◽  
Randomized Controlled ◽  
Literature Search Strategy ◽  
Previously Treated ◽  
Data Source

Abstract Abstract 1090 Background: The incidence of venous thromboembolism (VTE) in patients with multiple myeloma (MM) is high in patients treated with thalidomide (T)- and lenalidomide (L)-based regimens containing dexamethasone (D) and/or cytotoxic chemotherapy (C). Consensus guidelines recommend routine thromboprophylaxis but reliable data from randomized controlled trials are lacking. Recent observational studies have suggested that thromboprophylaxis might be efficacious in decreasing the risk of VTE in this population. Purpose: To determine the absolute rates of VTE with and without different thromboprophylactic agents (ASA, warfarin, low-molecular-weight-heparin [LMWH]) in patients with newly diagnosed or previously treated MM receiving T- or L-based regimens. Data Source: A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews of published studies up to Jan 2010. Results: A total of 66 studies were included in the analyses. Of these, 61 (4264 patients) and 5 (1119 patients) assessed T- and L-based regimens, respectively. Thalidomide-based regimens The rates of VTE (per 100 patient-cycles) in patients with newly diagnosed MM treated with T-based regimens: The rates of VTE (per 100 patient-months) in patients with previously treated MM managed with T-based regimens: Lenalidomide-based regimens The rates of VTE (per 100 patient-cycles) in patients with newly diagnosed MM treated with L-based regimens: The rate VTE (per 100 patient-months) in patients with previously treated MM managed with L-based regimens: None of the studies reported major bleeding events. Limitations: The definition for VTE varied across studies. Most studies did not outline the diagnostic criteria for VTE. Data are not available (NA) for all prophylaxis regimens. Conclusion: Patients with newly diagnosed or previously treated MM receiving T- or L-based regimens are at high risk of VTE. It is uncertain whether thromboprophylaxis provides a clear benefit, especially in those receiving L-based therapy or have previously treated disease. Randomized controlled trials are needed to address this important clinical need. Disclosures: Lee: Eisai: Research Funding; Sanofi Aventis: Consultancy, Honoraria; Leo Pharma: Consultancy; Pfizer: Consultancy, Honoraria; Bayer: Honoraria; Boehringer Ingelheim: Consultancy, Honoraria, Speakers Bureau.

Melphalan and Prednisone (MP) Versus Melphalan, Prednisone and Thalidomide (MPT) as Initial Therapy for Previously Untreated Elderly and/or Transplant Ineligible Patients with Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 615-615 ◽  
Author(s):  
Prashant Kapoor ◽  
S. Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
David Dingli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Randomized Controlled Trials ◽  
Research Funding ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
The Impact

Abstract Abstract 615 Background: Trials comparing efficacy of standard melphalan prednisone (MP) therapy with MP plus thalidomide (T) in the transplant ineligible, elderly patients with multiple myeloma have provided conflicting evidence. While there is greater agreement with regard to superior response rates (RR) with the addition of T to MP in elderly patients, the impact on progression free survival (PFS) and overall survival (OS) is less clear with some trials showing an improvement in PFS and/or OS with MPT and others demonstrating no difference in outcomes. We performed a systematic review to integrate the existing outcome data related to the efficacy of MP vs. MPT using a meta-analytic approach. Methods: A comprehensive search of electronic database through July 31st, 2009 was performed for publications, abstracts and presentations to identify randomized controlled trials (RCTs) comparing MP with MPT. A meta-analysis was performed by pooling results on clinical endpoints of RR, PFS and OS reported in all the identified RCTs under a random effects model. We did not have access to individual patient data from these trials. Results: Overall, five prospective RCTs (3 published articles and 2 abstracts) comparing MP with MPT regimen and comprising a total of 1571 patients were identified. For the endpoints of OS and PFS, data were extractable only from 4 RCTs (abstract by Gulbrandsen et al. was excluded). The Bregg and Egger funnel plot for OS demonstrated a symmetric distribution (P = 0.6) indicating no significant publication bias. The test of heterogeneity among all RCTs was statistically significant in the estimate of RR (tau2=0.21; chi2=16.33; p=0.003 (df=4); I2 = 75.5%), but not significant for the estimates of PFS (tau2=0.01; chi2=4.61; p=0.2 (df=3); I2 = 34.9%), and OS (tau2=0.02; chi2=5.53; p=0.14 (df=3); I2 = 45.8%). As expected, the pooled odds ratio of responding to treatment with MP versus MPT was 0.307 (P<0.001) indicating that MP was worse than MPT in achieving at least a partial response. The pooled hazard ratios (HR) for PFS and OS were 1.59 (p<0.001) and 1.34 (p=0.006), respectively (see table for forest plots) in favor of MPT. Conclusion: Our meta-analysis implies that in previously untreated, transplant ineligible elderly patients with multiple myeloma, the addition of thalidomide to melphalan-prednisone demonstrates improved RR, PFS and OS compared with the use of melphalan-prednisone alone. Although the results from a comprehensive individual patient data pooled analysis would give a more precise estimate, our analysis suggests that MPT is superior to MP in terms of response and survival. Disclosures: Dispenzieri: Celgene: Research Funding. Gertz:Celgene: Honoraria. Kumar:celgene, genzyme, millennium, novartis, bayer: Research Funding; genzyme: Membership on an entity's Board of Directors or advisory committees.

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

Systematic Review and Meta-Analysis of Randomized Controlled Trials of Erythropoietin in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 232-232
Author(s):  
Heloisa P. Soares ◽  
Ambuj Kumar ◽  
Franco Silvestris ◽  
Benjamin Djulbegovic
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Current Evidence ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Epoetin Alpha

Abstract Background: The current approach for treating anemia in multiple myeloma (MM) patients entails prescribing recombinant erythropoetin (EPO) only if chemotherapy fails initially to raise hemoglobin (Hb) levels. However, this practice is not based on synthesis of the totality of evidence obtained from data of all trials testing EPO exclusively in myeloma patients. Objective: To conduct a systematic review/ meta-analysis (SR/MA) regarding the use of EPO in MM patients. Methods: We conducted a SR of all randomized controlled trials (RCTs) that studied the effect of EPO exclusively in MM patients. We searched all major electronic databases (MEDLINE, LILACS, EMBASE and the Cochrane Controlled Trials Register) as well as performing hand searches of relevant meeting proceedings (ASH, ASCO, EHA), and ongoing NCI trials. We included RCTs that had at least 10 patients in each arm and had compared the use of EPO against a control group. We also identified trials that compared different doses of EPO. We excluded trials that enrolled patients treated with high-dose myeloablative chemotherapy followed by stem cell transplantation or hemodialysis. Results: We identified more than 500 relevant studies; 6 trials met our eligibility criteria and were included in the analysis. Five trials (4 published as full text manuscripts and 1 as the abstract) compared epoetin alpha against a control [placebo (2 trials) or no therapy with or without specification of red cells transfusion trigger level (3 trials)] in anemic MM patients. One trial compared 2 different schedules of epoetin alpha. No trial tested the effect of darbopoeitin. All 5 trials that studied EPO against controls used initial doses of 150 IU 3x/week SC with the possibility of increasing to 300 IU if necessary. In the majority of trials the patients had been receiving chemotherapy at the time EPO was administered. The number of patients included in each trial ranged from 24 to 145. All trials concluded that EPO was superior to a placebo or no treatment in terms of Hb increase. Two trials also concluded that EPO improves quality of life. Our meta-analysis showed that hematological response was favored in the group receiving EPO [relative risk (RR) 7.75; 95% CI 4.19 to 14.35, 4 trials, n = 272]. Mean Hb level improvement with EPO was also significant [weighted mean difference (WMD) 2.29; 95% CI2.00 to -2.58, 3 trials, n = 235]. In terms of adverse events, hypertension was more often found in the EPO arm [RR 5.80; 95% CI 1.30-25.90, 4 trials, n = 290]. Survival and data related to tumor response were not available in all trials. Critical appraisal indicated that available evidence was modest in quantity (5 trials, n= 385 total patients enrolled) and poorly reported in all important methodological domains. Conclusion: Available body of evidence suggests that EPO improves hematological outcomes in patients with myeloma. However, the quality of current evidence is insufficient, data on most important patients’ outcomes are lacking (e.g. survival etc.), thus preventing us from making definitive recommendations regarding the role of EPO in managing anemia in the myeloma setting. A definitive RCT to resolve the role of EPO in myeloma is indicated.

Sign in / Sign up

Export Citation Format

Share Document