scholarly journals 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 randomised controlled trials

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wu Ye ◽  
Xia Wu ◽  
Xiaoyan Liu ◽  
Xue Zheng ◽  
Jili Deng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Partial Response ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Grade 3 ◽  
Randomised Controlled

Abstract Background Many clinical trials have assessed the effect and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma (MM). The treatment outcomes of comparing different MAbs in combination with the above-mentioned agents remained unclear. We performed the meta-analysis to indirectly compare the effect and safety of MAbs targeting CD38, SLAMF7, and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for patients with MM. Methods We searched thoroughly in the databases for randomised controlled trials (RCTs) in which at least one of the three MAbs were included. We included eleven eligible RCTs with 5367 patients in the meta-analysis. Statistical analysis was carried out using StataMP14 and Indirect Treatment Comparisons software. Results We calculated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and 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 HRs 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 (95%CI 0.543–0.806), 0.317 (95%CI 0.221–0.454), and 0.479 (95%CI 0.328–0.699), respectively. The HR for OS of the CD38 group vs SLAMF7 group was 0.812 (95%CI 0.584–1.127). The RR for CR or better in the CD38 group vs SLAMF7 group was 2.253 (95%CI 1.284–3.955). The RR for neutropenia of the CD38 group vs SLAMF7 group was 1.818 (95%CI 1.41–2.344). Conclusions Treatment with the CD38 group had longer PFS and better treatment response than that with the SLAMF7 or PD-1/PD-L1 group. In addition, the SLAMF7 group prolonged PFS compared with the PD-1/PD-L1 group and was associated with a lower incidence of grade 3 or higher neutropenia than the CD38 and PD-1/PD-L1 group. In conclusion, MAbs targeting CD38 are the best, followed by those targeting SLAMF7; MAbs targeting PD-1/PD-L1 are the worst when in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for the treatment of MM.

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 Monoclonal Antibodies versus Histone Deacetylase Inhibitors in Combination with Bortezomib or Lenalidomide plus Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma: An Indirect-Comparison Meta-Analysis of Randomized Controlled Trials

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Yanhua Zheng ◽  
Hongyuan Shen ◽  
Li Xu ◽  
Juan Feng ◽  
Hailong Tang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Complete Response ◽  
Refractory Multiple Myeloma ◽  
Grade 3

During the past decades, agents with novel mechanisms of action, such as monoclonal antibodies (MAbs) and histone deacetylase inhibitors (HDACis) have been applied to treat relapsed or refractory multiple myeloma (RRMM). The treatment outcomes of MAbs versus HDACi in combination with bortezomib or lenalidomide plus dexamethasone remain unknown. We conducted this meta-analysis to compare indirectly the efficacy and safety of MAbs and HDACis in combination with bortezomib or lenalidomide plus dexamethasone. Six trials (eight articles) were included in the meta-analysis with 3270 RRMM patients enrolled. We synthesized hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) for complete response (CR),very good partial response (VGPR), overall response (OR), progressive disease plus stable disease (PD + SD) and common at least grade 3 adverse events, and their corresponding 95%confidence intervals (95% CI). Treatment with MAbs in combination with bortezomib or lenalidomide plus dexamethasone resulted in longer PFS (HR 0.83, 95% CI: 0.66–0.98), fewer incidences of at least grade 3 thrombocytopenia (RR 0.35, 95% CI: 0.23–0.53), neutropenia (RR 0.70, 95% CI: 0.51–0.96), and sense of fatigue (RR 0.37, 95% CI: 0.17–0.82) than HDACis. The daratumumab plus bortezomib or lenalidomide and dexamethasone might significantly improve PFS in comparison with HDACis plus bortezomib or lenalidomide and dexamethasone (HR 0.55, 95% CI: 0.40–0.74). In conclusion, MAbs may be superior to HDACis in achieving longer PFS and may be better tolerated when in combination therapy with bortezomib or lenalidomide plus dexamethasone.

scholarly journals Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Szabolcs Kiss ◽  
Noémi Gede ◽  
Péter Hegyi ◽  
Bettina Nagy ◽  
Rita Deák ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Randomised Controlled Trials ◽  
Residual Disease ◽  
Meta Analysis ◽  
Complete Response ◽  
Controlled Trials ◽  
Newly Diagnosed ◽  
Hazard Ratios ◽  
Randomised Controlled

AbstractDaratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33–5.61)] and sCR [OR = 2.29 (CI 1.49–3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39–0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76–10.66)] and sCR [OR = 3.08 (CI 2.00–4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37–0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.

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.

scholarly journals Efficacy of vision-based treatments for children and teens with amblyopia: a systematic review and meta-analysis of randomised controlled trials

2021 ◽  
Vol 6 (1) ◽  
pp. e000657
Author(s):  
Taylor Adrian Brin ◽  
Amy Chow ◽  
Caitlin Carter ◽  
Mark Oremus ◽  
William Bobier ◽  
...  
Keyword(s):  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Linear Regression Analysis ◽  
Treatment Success ◽  
Indirect Comparison ◽  
Mean Difference ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Standard Mean Difference ◽  
Randomised Controlled

ObjectiveTo identify differences in efficacy between vision-based treatments for improving visual acuity (VA) of the amblyopic eye in persons aged 4–17 years old.Data sourcesOvid Embase, PubMed (Medline), the Cochrane Library, Vision Cite and Scopus were systematically searched from 1975 to 17 June 2020.MethodsTwo independent reviewers screened search results for randomised controlled trials of vision-based amblyopia treatments that specified change in amblyopic eye VA (logMAR) as the primary outcome measure. Quality was assessed via risk of bias and GRADE (Grading of Recommendations, Assessment, Development, and Evaluations).ResultsOf the 3346 studies identified, 36 were included in a narrative synthesis. A random effects meta-analysis (five studies) compared the efficacy of binocular treatments versus patching: mean difference −0.03 logMAR; 95% CI 0.01 to 0.04 (p<0.001), favouring patching. An exploratory study-level regression (18 studies) showed no statistically significant differences between vision-based treatments and a reference group of 2–5 hours of patching. Age, sample size and pre-randomisation optical treatment were not statistically significantly associated with changes in amblyopic eye acuity. A network meta-analysis (26 studies) comparing vision-based treatments to patching 2–5 hours found one statistically significant comparison, namely, the favouring of a combination of two treatment arms comparing combination and binocular treatments, against patching 2–5 hours: standard mean difference: 2.63; 95% CI 1.18 to 4.09. However, this result was an indirect comparison calculated from a single study. A linear regression analysis (17 studies) found a significant relationship between adherence and effect size, but the model did not completely fit the data: regression coefficient 0.022; 95% CI 0.004 to 0.040 (p=0.02).ConclusionWe found no clinically relevant differences in treatment efficacy between the treatments included in this review. Adherence to the prescribed hours of treatment varied considerably and may have had an effect on treatment success.

scholarly journals Risk of Serious Infections with Lenalidomide Based Regimens in Multiple Myeloma: A Network Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-12
Author(s):  
Nayab Mirza ◽  
Anum Javaid ◽  
Muhammad Ashar Ali ◽  
Wajeeha Aiman ◽  
Muhammad Yasir Anwar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Maintenance Therapy ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
High Grade ◽  
Serious Infections ◽  
Grade 3

Background: Lenalidomide is an immune modulator, approved for use since 2005 for the treatment of multiple myeloma (MM) patients. Its use is associated with an increased risk of infections. Combination of lenalidomide with other drugs, monoclonal antibodies, proteasome inhibitors, dexamethasone, and alkylators, can enhance the risk of serious infections. We conducted a network meta-analysis to compare the incidence of ≥Grade 3 infections among lenalidomide based regimens used in MM that can help clinicians to monitor patients for the risk of infections. Methods: A search was performed on PubMed, Cochrane, Embase, and Web of Science. We used the following keywords, "lenalidomide" AND "multiple myeloma" from the inception of literature till 06/10/2020. We screened 14,684 articles and included 23 randomized clinical trials (RCT) (N=11,174) in network meta-analysis. We extracted the data for serious (≥Grade 3) infections in lenalidomide based regimens. We excluded case reports, case series, preclinical trials, non-randomized clinical trials, observational studies, review articles, meta-analysis, and RCTs not providing any information about ≥Grade 3 infections. We used the "netmeta" package by Rucker et al. in the R programming language (version 4.0.2) to conduct frequentist network meta-analysis. Results: In 23 RCTs, the median age was ≥65years in 11 RCTs (N=5585) and ≤65 in 12 RCTs (5589). 9 RCTs were performed on relapsed/refractory multiple myeloma (RRMM) patients (N=4254), while 13 RCTs were performed on newly diagnosed multiple myeloma (NDMM) patients (N=6920). Lenalidomide regimen was used as maintenance therapy in 8 RCT (N=4255). Table 1 reviews the baseline characteristics. The pooled incidence of high-grade infections in trials with a median age of ≥65 and ≤65 years is 1010/5585 and 634/5589, respectively. The incidence of high-grade infections is 693/4254 in RRMM patients, 951/6920 in NDMM patients, and 466/4255 in NDMM patients with maintenance therapy. P-score in table 2 represents the mean extent of certainty with which a regimen is better in terms of the incidence of high-grade infections, i.e., higher P-score means a lower risk of serious infections. According to P-score, lenalidomide with carfilzomib and dexamethasone is worst in terms of the incidence of infections. Indirect comparison of placebo with lenalidomide shows a risk ratio of high-grade infections of 2.87 (95% CI: 1.96; 4.23) in favor of placebo. Fig 1 outlines the indirect comparison of the incidence of high-grade infections with different lenalidomide based regimens vs. placebo. Table 3. shows the calculated indirect comparison of high-grade infections in each lenalidomide based regimen. Heterogeneity was not statistically significant. For serious infections, lenalidomide dexamethasone showed a risk ratio of 0.86, 0.70*, 0.76*, 0.78*, 0.77, and 0.77 in comparison with the combination of lenalidomide dexamethasone with bortezomib, carfilzomib, daratumumab, elotuzumab, ixazomib, and pembrolizumab respectively (*statistically significant). Conclusion: This network meta-analysis suggests an increase in the risk of high-grade infections with the addition of bortezomib, monoclonal antibodies, ixazomib, and carfilzomib to lenalidomide in multiple myeloma patients with the highest increase in risk with the addition of carfilzomib. Additional randomized clinical trials are needed on the toxicity of lenalidomide based regimens to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Safety And Cardiovascular Efficacy Of Anti-Pcsk9 Monoclonal Antibodies: A Meta-Analysis Of Randomised Controlled Trials

2019 ◽  
Vol 287 ◽  
pp. e39 ◽  
Author(s):  
M. Casula ◽  
E. Olmastroni ◽  
M. Boccalari Taddeo ◽  
E. Tragni ◽  
A. Pirillo ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomised Controlled

scholarly journals A Systematic Review and Network Meta-Analysis of Randomized Data on Efficacy of Novel Therapy Combinations in Patients with Lenalidomide Refractory Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-12
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Jill Hampton ◽  
Muhammad Aziz ◽  
Sadik Khuder ◽  
Saad Ullah Malik ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Significant Heterogeneity ◽  
Free Survival ◽  
Treatment Regimens ◽  
Randomized Controlled

Introduction: Advancements in the treatment of multiple myeloma (MM) with proteasome inhibitors [bortezomib (bort), carfilzomib (carf)], monoclonal antibodies [daratumumab (dara), isatuximab (isa) and elotozumab (elo)], and immunomodulatory drugs [IMiD) [lenalidomide and pomalidomide (pom)] have improved outcomes. However, using lenalidomide as frontline treatment and maintenance therapy exposes greater numbers of patients to lenalidomide prior to relapse. Consequently, the treatment of lenalidomide-refractory (LR) disease is an increasing area of concern. Given the lack of direct comparisons of different treatment regimens for LR MM, we used a systematic review to identify randomized controlled trials (RCTs) that included subgroup analysis of LR patients. The objective of our study was to compare the efficacy of novel treatment regimens in randomized trials for patients with LR MM using a network meta-analysis. Methods: Three databases were searched: MEDLINE/PubMed, Embase, and Cochrane Registry of Controlled Trials. All studies published between January 1, 2005 and December 30, 2019 were queried using keywords "multiple myeloma" and "randomized controlled trial". Only RCT's were included. Primary outcome was progression free survival (PFS) of patients enrolled in myeloma RCT's. Two independent investigators reviewed all the studies and resolved any conflict through mutual discussion. WNetwork meta-analysis using random-effects model was performed to generate direct and indirect comparisons between various treatment groups. Frequentist method was used to rank the interventions and P-score was generated. A higher P score (close to 1.00) corresponded to superior progression free survival. A P-value of &lt;0.05 was considered statistically significant. Hazard ratios (HR) with 95% confidence interval (CI) were calculated. I2statistic was used to assess heterogeneity between the studies as defined by the Cochrane Handbook for Systematic Reviews with a value &gt;50% considered as significant heterogeneity. We used 'R' (Bell Labs, Murray Hill, NJ, USA) for generating our statistical analysis and plots. Results: Our initial search strategy yielded 1171 results. After excluding duplicates, trials in progress, subset analysis and non-randomized studies, 123 RCTs were identified. Only 8 studies clearly reported outcomes of patients with LR myeloma and 7 studies (1698 patients) were included in final analysis of two discrete networks. Pom/bort/dex (HR: 0.65,95% CI: 0.50-0.84), dara/bort/dex (HR: 0.36, 95% CI: 0.21-0.63), and dara/carf/dex (HR: 0.38, 95% CI: 0.21-0.69) were all found to have improved PFS compared to bort/dex (Figure 2). These interventions were ranked as follows: Dara-bort-dex was the most efficacious with a P-score of 0.8758, followed by Dara/carf/Dex (P of 0.8514), Pom/bort/dex (P of 0.4791), Carf/dex (P of 0.2707) and Bort/dex (P of 0.0231). Within Network 2 (Figure 3), pom/dex (HR :0.50, 95% CI= 0.40-0.62), isa/pom/dex (HR: 0.30, 95% CI= 0.20-0.44) and elo/pom/dex (HR: 0.27, 95% CI=0.16-0.45), were all found to have improved PFS compared to dexamethasone (Figure 4). In Network 2, the ranking of interventions was as follows with Elo-pom-dex (P of 0.8716) the most efficacious, followed by Isa-pom-Dex (P of 0.7932) and Pom-dex (P of 0.3352). Conclusion: The results of our network meta-analysis of 1698 patients with lenalidomide refractory myeloma enrolled in seven randomized myeloma trials demonstrate that for lenalidomide refractory myeloma, triplet therapy is superior to doublet therapy. Regimens with the highest efficacy in this subset of patients were triplets containing monoclonal antibodies (such as dara/elo/isa). There is a need for further randomized data to better ascertain the best standard of care for these patients. Disclosures No relevant conflicts of interest to declare.

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