scholarly journals Efficacy and Safety of Daratumumab Based Regimens for Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3292-3292
Author(s):  
Muhammad Abu Zar ◽  
Ahmad Kamal ◽  
Ali Younas Khan ◽  
Saad Ullah Malik ◽  
Mustafa Nadeem Malik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Drug Regimen ◽  
Cochrane Library ◽  
Extensive Literature ◽  
Efficacy And Safety ◽  
Grade 3 ◽  
Line Of Therapy

Abstract Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 that has been approved for the treatment of multiple myeloma (MM). We performed a meta-analysis of trials with daratumumab to find its efficacy and safety. Materials and Methods: Extensive literature search of Medline, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov on 5/07/2018 identified a total of 1596 articles. Fourteen articles (n = 1439) met the inclusion criteria, eleven in the relapsed and refractory multiple myeloma (RRMM) and three in the newly diagnosed multiple myeloma (NDMM) group (Table 1). A meta-analysis was performed using STATA version 15 and inter study heterogeneity was calculated using I² statistic. Results: The overall response rate (ORR) was 69% (95% CI: 51-84%) and very good partial response or better (≥VGPR) was 40% (95% CI: 22-60%) in RRMM patients. In a subgroup analysis with three, two and single drug regimen, ORR was 85% (95% CI: 77-92%), 30% (95% CI: 21-40%) and 31% (95% CI: 24-39%) respectively in RRMM patients. The hazard ratio (HR) for progression free survival (PFS) with daratumumab based regimens was 0.35 (95% CI: 0.26-0.45) as compared to non-daratumumab based regimens in two randomized controlled trials (RCTs). The most effective regimen, in terms of PFS for RRMM patients with a median of a single previous line of therapy was daratumumab with lenalidomide with dexamethasone (24-months PFS rate: 68%) in the POLLUX trial (Dimopoulos et al., 2017). The ORR was 97% (95% CI: 92-100%) and ≥VGPR rate was 64% (95% CI: 44-83%) in NDMM patients (Figure 1). In the only available RCT for NDMM patients, the HR for PFS was 0.50 (95% CI: 0.38-0.65) (Mateos et al., 2017). Incidence of neutropenia was 30% (95% CI: 16-46%) and thrombocytopenia was 25% (95% CI: 15-37%). While the incidence of anemia was 17% (95% CI: 13-21%). Incidence of ≥ grade 3 non-hematologic treatment emergent adverse effects (TEAEs) were as follows: pneumonia (11.3-12%), hypertension (8-12%) and fatigue (4-12.5%). In daratumumab and non-daratumumab based regimens ≥ grade 3 infusions related reactions occurred in 5% of the patients. In the three RCTs, these hematologic (≥ grade 3) TEAEs were comparable as neutropenia occurred in 36.86% vs 29.57%, thrombocytopenia in 30% vs 29% and anemia in 16.67% vs 19% respectively. Patients on daratumumab based regimens who discontinued treatment due to TEAEs were 8.56% vs 9.93% on non-daratumumab based regimens in the three RCTs which shows that most of the treatment discontinuations was due to other drugs in the regimen. Conclusion: Our results suggest that daratumumab containing regimen is more effective than non-daratumumab based regimens for RRMM and NDMM patients. Three drug daratumumab based regimens are more effective when compared to two drug or daratumumab monotherapy regimens. The safety profile of daratumumab is favorable, which makes it an extremely useful drug. Despite limited data in NDMM patients, daratumumab based regimens appear to be highly effective. Further prospective randomized trials are needed to compare various daratumumab based regimens. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis

2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110381
Author(s):  
Yin Wang ◽  
Yanqing Li ◽  
Ye Chai
Keyword(s):  
Multiple Myeloma ◽  
Meta Analysis ◽  
Complete Response ◽  
Library Science ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Risk Patients ◽  
Grade 3 ◽  
Combination Regimens

Objective To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). Methods A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. Results A total of seven RCTs were included ( n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. Conclusion The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.

The Efficacy and Safety of Immunomodulatory Drugs in Multiple Myeloma Maintenance Therapy: Results of a Meta-Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3477-3477
Author(s):  
Yucai Wang ◽  
Fang Yang ◽  
Wenwen Zhang ◽  
Xiaoxiang Guan ◽  
Neil Kothari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Immunomodulatory Drugs ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Abstract Objective: To evaluate the efficacy and safety of immunomodulatory drugs (IMiDs) in maintenance therapy of multiple myeloma through meta-analysis of randomized controlled trials (RCTs). Patients and methods: PubMed, Web of Science, ASCO, ESMO and ASH databases were searched for RCTs that investigated the treatment outcomes (overall survival [OS], progression-free survival [PFS] and/or event-free survival [EFS] and/or time to progression [TTP]) of maintenance therapy with IMiDs in patients with multiple myeloma. Study endpoints included OS, PFS/EFS/TTP, and grade 3 or 4 adverse events. Pooled hazard ratios (HRs) for survival outcomes and risk ratios (RRs) for dichotomous data with 95% confidence interval (CI) were calculated using Comprehensive MetaAnalysis (v2). The random-effect model was utilized in view of clinical heterogeneity in the study population. Results: Eighteen RCTs comprising a total of 6562 patients were included in this meta-analysis. IMiDs used in the RCTs included thalidomide (14 trials) and lenalidomide (4 trials). Overall, IMiD-based maintenance therapy significantly improved OS (HR = 0.91, 95% CI = 0.84 - 0.99, P = 0.027) and PFS (HR = 0.63, 95% CI = 0.60 - 0.68, P < 0.001). Notably, IMiDs maintenance therapy increased OS in the setting of ASCT but showed no OS prolongation without ASCT. On further stratification, thalidomide-based maintenance therapy demonstrated OS benefit only in the setting of ASCT, while lenalidomide-based maintenance therapy did not show OS benefit regardless of transplantation status. For PFS however, both thalidomide- and lenalidomide-based maintenance therapies demonstrated significant survival benefits, regardless of transplantation status (Table 1). IMiD-based maintenance therapy increased the risk of developing grade 3 or 4 neutropenia (RR = 3.04, 95% CI = 2.49 - 3.70, P < 0.001), thrombocytopenia (RR = 2.68, 95% CI = 1.90 - 3.79, P < 0.001), anemia (RR = 1.97, 95% CI = 1.23 - 3.15, P = 0.005), infection (RR = 1.53, 95% CI = 1.22 - 1.92, P < 0.001), fatigue (HR = 1.71, 95% CI = 1.24 - 2.36, P = 0.001), constipation (RR = 2.04, 95% CI = 1.15 - 3.62, P = 0.015), and peripheral neuropathy (RR = 2.02, 95% CI = 1.20 - 3.39, P = 0.008). Conclusions: IMiD-based maintenance therapy results in significant improvement in OS and PFS in multiple myeloma patients but increased the risk of developing some grade 3 or 4 adverse events. While thalidomide-containing maintenance therapy regimens showed OS benefits in the setting of ASCT, lenalidomide-containing maintenance therapy did not prolong OS regardless of transplantation status. Both thalidomide- and lenalidomide-based maintenance therapies increased PFS in multiple myeloma patients independent of transplantation status. When more data on lenalidomide and the newer agent pomalidomide become available, further analysis will be warranted to analyze the efficacy and safety of IMiDs in multiple myeloma maintenance therapy. Table 1. Effects of IMiD-based maintenance therapy on OS and PFS in multiple myeloma patients IMiD ASCT status Survival Number of trials HR 95% CI P value Thalidomide/Lenalidomide combined OS 18 0.91 0.84 - 0.99 0.027 with ASCT OS 10 0.88 0.78 - 0.99 0.036 without ASCT OS 9 0.94 0.83 - 1.06 0.299 Thalidomide combined OS 14 0.92 0.84 - 1.01 0.090 with ASCT OS 8 0.87 0.77 - 1.00 0.049 without ASCT OS 7 0.97 0.85 - 1.10 0.640 Lenalidomide combined OS 4 0.84 0.67 - 1.04 0.102 with ASCT OS 2 0.89 0.66 - 1.20 0.457 without ASCT OS 2 0.78 0.57 - 1.06 0.114 Thalidomide/Lenalidomide combined PFS 17 0.63 0.60 -0.68 < 0.001 with ASCT PFS 9 0.62 0.57 - 0.67 < 0.001 without ASCT PFS 9 0.66 0.60 - 0.73 < 0.001 Thalidomide combined PFS 13 0.67 0.63 - 0.72 < 0.001 with ASCT PFS 7 0.66 0.60 - 0.72 < 0.001 without ASCT PFS 7 0.69 0.62 -0.77 < 0.001 Lenalidomide combined PFS 4 0.50 0.43 - 0.58 < 0.001 with ASCT PFS 2 0.49 0.41 - 0.58 < 0.001 without ASCT PFS 2 0.52 0.40 - 0.67 < 0.001 Disclosures No relevant conflicts of interest to declare.

Efficacy and Safety of Bortezomib Based Regimens Retreatment in Relapsed Multiple Myeloma Patients: Results from a Retrospective Study.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5387-5387
Author(s):  
Wenjun Wu ◽  
Gaofeng Zheng ◽  
Xiaoyan Han ◽  
Yi Zhao ◽  
Donghua He ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Confidence Interval ◽  
Incidence Rate ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Efficacy And Safety ◽  
Grade 3 ◽  
Group 1

Abstract Objective: To evaluate the efficacy and safety of bortezomib retreatment in relapsed multiple myeloma (MM) patients, who previously responded to bortezomib. Methods: This retrospective observational study included data from 45 patients and evaluated the efficacy and safety of bortezomib based retreatment in these patients, who had achieved at least a partial response (PR) on initial bortezomib therapy in our hospital from May 2006 to May 2013. Results: The overall response rate (ORR) was 71.2%, among them 9% patients achieved CR, 11.1% patients achieved very good partial response (VGPR), 51.1% patients achieved PR. All patients were divided into 3 groups according to the response of initial bortezomib therapy, including CR group, VGPR group and PR group. After bortezomib retreatment, the ORR of the 3 groups was 76.9%, 75% and 62.5%, respectively. According to the response of bortezomib retreatment, the patients were divided into 2 groups: group 1 who at least achieved PR, group 2 who showed no response. The median progression-free survival (PFS) after bortezomib retreatment for group 1 and 2 was 9( 95% confidence interval 7.947~10.051) and 10 (95% confidence interval 8.381∼11.619) months, respectively (P>0.05), while the median overall survival (OS) after bortezomib retreatment was 71 (95% confidence interval 66.694∼75.306)) and 37 (95% confidence interval 1-28) months, respectively (P<0.05). In patients with bortezomib retreatment had different degrees of adverse events (AE) , the most AE for grade 1~2. The most common grade ≥3 AE was thrombocytopenia, neutropenia and anemia. The incidence rate of grade ≥3 AE peripheral neuropathy bortezomib was 15%. Conclusion: Bortezomib based regimens retreatment was effective and tolerable in relapsed MM patients, who had achieved at least a partial response (PR) on initial therapy. The incidence rate of AE was not significantly increased. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy and safety of bortezomib maintenance in patients with newly diagnosed multiple myeloma: a meta-analysis

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Chun-yan Sun ◽  
Jun-ying Li ◽  
Zhang-bo Chu ◽  
Lu Zhang ◽  
Lei Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Increased Risk ◽  
The Cochrane Library

Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here, we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID), and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both progression-free survival (PFS) (hazard ratio (HR) 0.67, 95% confidence interval (CI) = 0.51 to 0.87, P=0.003) and overall survival (OS) (HR = 0.75 therapy, 95% CI = 0.63 to 0.89, P=0.001) more than did non-bortezomib maintenance therapy. Our analysis revealed higher incidence of neutropenia (risks ratios (RR) = 1.39; 95% CI = 1.08 to 1.79), peripheral neuropathy (PN) (RR = 2.23; 95% CI = 1.38 to 3.61, P=0.001), and cardiologic events (RR = 1.91; 95% CI = 1.12 to 3.28, P=0.02) in patients with bortezomib maintenance therapy. Our meta-analysis demonstrates OS and PFS benefits of bortezomib maintenance therapy in patients with newly diagnosed MM. However, the therapy is associated with increased risk of adverse events. Additionally, more RCTs are needed for better understanding and determination of optimal bortezomib maintenance therapy in MM.

scholarly journals Safety and Efficacy of Anti-PD-1/PD-L1 Inhibitors Compared With Docetaxel for NSCLC: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Long Ma ◽  
Gang Jin ◽  
Keying Yao ◽  
Yi Yang ◽  
Ruitong Chang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
High Quality Research ◽  
Free Survival ◽  
Randomized Controlled ◽  
Grade 3 ◽  
Docetaxel Chemotherapy

Objective: To evaluate the efficacy and safety of anti-PD-1/PD-L1 Inhibitors versus docetaxel for non-small cell lung cancer by meta-analysis.Methods: Randomized controlled trials (RCTs) about anti-PD-1/PD-L1 Inhibitors versus docetaxel on the treatment of NSCLC were searched in CNKI, WF, VIP, PubMed, EMBASE, Cochrane Library, and Web of Science databases. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of eligible studies. Meta-analysis was performed by RevMan5.3 software.Results: Compared with the use of docetaxel chemotherapy for NSCLC, the overall survival and progression-free survival of the anti-PD-1/PD-L1 Inhibitors regimen are better [overall survival: (HR= 0.73, 95%CI:0.69∼0.77, P&lt;0.00001], progression-free survival: (HR= 0.89, 95%CI:0.83∼0.94, P&lt;0.00001]), and lower incidence of treatment-related grade 3 or higher adverse events ([OR=0.20, 95% CI: 0.13∼0.31, P&lt;0.00001]).Conclusion: Compared with the docetaxel chemotherapy regimen, the anti-PD-1/PD-L1 Inhibitors has certain advantages in terms of efficacy and safety. The results still need to be confirmed by a multi-center, large sample, and high-quality research.

Bortezomib-Containing Regimens for Multiple Myeloma Maintenance Therapy: a Meta-Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3473-3473
Author(s):  
Yucai Wang ◽  
Wenwen Zhang ◽  
Fang Yang ◽  
Xiaoxiang Guan ◽  
Neil Kothari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
High Dose ◽  
Vascular Events ◽  
Cardiac Disorders ◽  
Grade 3

Abstract Objective: To evaluate the efficacy and safety of bortezomib-containing regimens in maintenance therapy of multiple myeloma through meta-analysis of randomized controlled trials (RCTs). Patients and methods: PubMed, Web of Science and ASH databases were searched for RCTs that investigated the treatment outcomes (progression-free survival [PFS] and overall survival [OS]) of maintenance therapy with bortezomib-containing regimens in patients with multiple myeloma. Study endpoints included PFS, OS, and grade 3 or 4 adverse events. Pooled hazard ratios (HRs) for survival outcomes and risk ratios (RRs) for dichotomous data with 95% confidence interval (CI) were calculated using Comprehensive MetaAnalysis (v2). Results: Three RCTs comprising 1396 patients were included in this meta-analysis. Compared with maintenance therapy without bortezomib and/or no maintenance therapy, bortezomib-based maintenance therapy regimens significantly prolonged PFS (HR = 0.66, 95% CI = 0.58 - 0.76, P < 0.001) and OS (HR = 0.74, 95% CI = 0.62 - 0.88, P = 0.001) in multiple myeloma patients. In patients who received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT), bortezomib-based maintenance therapy increased both PFS (HR = 0.73, 95% CI = 0.61 - 0.86, P < 0.001) and OS (HR = 0.76, 95% CI = 0.61 - 0.95, P = 0.016). For transplant ineligible patients, maintenance therapy with bortezomib-containing regimen also increased PFS (HR = 0.58, 95% CI = 0.47 - 0.71, P < 0.001) and OS (HR = 0.70, 95% CI = 0.52 - 0.92, P = 0.012). However, bortezomib-based maintenance therapy increased the risks of grade 3 or 4 adverse events including thrombocytopenia (RR = 1.37, 95% CI = 1.01 - 1.87, P = 0.046), infections (RR = 1.29, 95% CI = 1.02 - 1.64, P = 0.035), cardiac disorders (RR = 2.01, 95% CI = 1.17 - 3.47, P = 0.012), and vascular events (RR = 2.02, 95% CI = 1.15 - 1.45, P= 0.015). Conclusions: Bortezomib-based maintenance therapy results in significant improvement in PFS and OS in multiple myeloma patients, but may increase the risk of developing some grade 3 or 4 adverse events, such as thrombocytopenia, infections, cardiac disorders, and vascular events. Further studies are needed to corroborate the above findings given the limited data on proteasome inhibitor based maintenance therapy for multiple myeloma. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy and safety of combined androgen blockade with antiandrogen for advanced prostate cancer

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Y. Yang ◽  
R. Chen ◽  
T. Sun ◽  
L. Zhao ◽  
F. Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
First Line ◽  
Combined Androgen Blockade ◽  
Hazard Ratios ◽  
Significant Difference ◽  
Grade 3 ◽  
Androgen Blockade

Background Combined androgen blockade (cab) is a promising treatment modality for prostate cancer (pca). In the present meta-analysis, we compared the efficacy and safety of first-line cab using an antiandrogen (aa) with castration monotherapy in patients with advanced pca.Methods PubMed, embase, Cochrane, and Google Scholar were searched for randomized controlled trials (rcts) published through 12 December 2016. Hazard ratios (hrs) with 95% confidence intervals (cis) were determined for primary outcomes: overall survival (os) and progression-free survival (pfs). Subgroup analyses were performed for Western compared with Eastern patients and use of a nonsteroidal aa (nsaa) compared with a steroidal aa (saa).Results Compared with castration monotherapy, cab using an aa was associated with significantly improved os (n = 14; hr: 0.90; 95% ci: 0.84 to 0.97; p = 0.003) and pfs (n = 13; hr: 0.89; 95% ci: 0.80 to 1.00; p = 0.04). No significant difference in os (p = 0.71) and pfs (p = 0.49) was observed between the Western and Eastern patients. Compared with castration monotherapy, cab using a nsaa was associated with significantly improved os (hr: 0.88; 95% ci: 0.82 to 0.95; p = 0.0009) and pfs (hr: 0.85; 95% ci: 0.73 to 0.98; p = 0.007)—a result that was not achieved with cab using a saa. The safety profiles of cab and monotherapy were similar in terms of adverse events, including hot flushes, impotence, and grade 3 or 4 events, with the exception of risk of diarrhea and liver dysfunction or elevation in liver enzymes, which were statistically greater with cab using an aa.Conclusions Compared with castration monotherapy, first-line cab therapy with an aa, especially a nsaa, resulted in significantly improved os and pfs, and had an acceptable safety profile in patients with advanced pca.

scholarly journals Combining Correlated Outcomes and Surrogate Endpoints in a Network Meta-Analysis of Colorectal Cancer Treatments

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2663
Author(s):  
Tung Hoang ◽  
Jeongseon Kim
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Cancer Treatments ◽  
Free Survival ◽  
Hazard Ratios ◽  
Credible Intervals ◽  
Grade 3 ◽  
Selection Of

This study aimed to investigate the efficacy and safety of systemic therapies in the treatment of unresectable advanced or metastatic colorectal cancer. Predicted hazard ratios (HRs) and their 95% credible intervals (CrIs) for overall survival (OS) were calculated from the odds ratio (OR) for the overall response rate and/or HR for progression-free survival using multivariate random effects (MVRE) models. We performed a network meta-analysis (NMA) of 49 articles to compare the efficacy and safety of FOLFOX/FOLFIRI±bevacizumab (Bmab)/cetuximab (Cmab)/panitumumab (Pmab), and FOLFOXIRI/CAPEOX±Bmab. The NMA showed significant OS improvement with FOLFOX, FOLFOX+Cmab, and FOLFIRI+Cmab compared with that of FOLFIRI (HR = 0.84, 95% CrI = 0.73–0.98; HR = 0.76, 95% CrI = 0.62–0.94; HR = 0.80, 95% CrI = 0.66–0.96, respectively), as well as with FOLFOX+Cmab and FOLFIRI+Cmab compared with that of FOLFOXIRI (HR = 0.69, 95% CrI = 0.51–0.94 and HR = 0.73, 95% CrI = 0.54–0.97, respectively). The odds of adverse events grade ≥3 were significantly higher for FOLFOX+Cmab vs. FOLFIRI+Bmab (OR = 2.34, 95% CrI = 1.01–4.66). Higher odds of events were observed for FOLFIRI+Pmab in comparison with FOLFIRI (OR = 2.16, 95% CrI = 1.09–3.84) and FOLFIRI+Bmab (OR = 3.14, 95% CrI = 1.51–5.89). FOLFOX+Cmab and FOLFIRI+Bmab showed high probabilities of being first- and second-line treatments in terms of the efficacy and safety, respectively. The findings of the efficacy and safety comparisons may support the selection of appropriate treatments in clinical practice. PROSPERO registration: CRD42020153640.

scholarly journals Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Progression Free Survival ◽  
The Other ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

scholarly journals Pomalidomide Based Regimens for Treatment of Relapsed Multiple Myeloma: A Systematic Review and Meta-Analysis of Clinical Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2022-2022
Author(s):  
Adeela Mushtaq ◽  
Ahmad Iftikhar ◽  
Midhat Lakhani ◽  
Fnu Sagar ◽  
Ahmad Kamal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Significant Heterogeneity ◽  
Grade 3 ◽  
Stratified Analysis

Abstract Introduction Bortezomib, a proteasome inhibitor and lenalidomide (Len), an immunomodulatory drug are the backbone of established treatment regimens for newly diagnosed MM. Patients with dual-refractory (refractory to both bortezomib and lenalidomide) disease have a poor prognosis with overall survival estimated to be less than one year. Pomalidomide (Pom) has distinct anticancer, antiangiogenic and immunomodulatory properties and has demonstrated synergistic antiproliferative activity in combination regimens. The aim of our study is to compare different Pom based regimens to identify the most effective regimen for relapsed refractory multiple myeloma (RRMM) patients. Methods A comprehensive literature search was performed on PubMed, Cochrane library, Web of Science, Embase and AdisInsight databases on 03/29/2018 which identified a total of 1374 studies. We included phase II/III clinical trials on pomalidomide based regimens that have clearly documented efficacy outcomes. All statistical analyses were performed using Comprehensive Meta-analysis (CMA) Version 3. We used the Cochrane Q statistics (p<0.05 considered significant) and I2 index to calculate the degree of heterogeneity of the studies. A random effect model was used if there was significant heterogeneity (p>0.05 or I2 >50%). Studies were classified into subgroups according to the therapeutic regimen: dual and triplet combinations. A separate stratified analysis of triplet regimens based on type of regimen was also performed. Results A total of 35 studies (n = 4623 patients) were included. The most commonly studied regimen was Pom + LoDex (Low dose dexamethasone) with a total of 16 studies on this regimen. All patients included in our study had ≥ 2 prior lines of therapy. Mean number of prior lines of therapy was 6. Most patients were lenalidomide refractory, with 10 patient cohorts of 100% refractoriness and 8 cohorts of ≥ 90% refractoriness. Pooled analysis showed an overall response rate (ORR) of 47.1% across all Pom regimens including both doublet and triplet regimens. An I2 value of 87.3 was found, indicating high heterogeneity across all Pom regimens. With Pom-LoDex, pooled ORR was found to be 35.7% and mean OS 14.37 months. With triplet regimens, pooled ORR was found to be 61.9%. In a separate stratified analysis of triplet regimens based on type of regimen, pooled ORRs with few selected regimens were as follows; Bort-Pom-LoDex (pooled ORR 83.5%, mean PFS 15.7 months [mos]), CFZ-Pom-LoDex (pooled ORR 77.1%, mean PFS 15.3 mos), Pom-LoDex-bendamustine (pooled ORR 74.2%), Pom-Dex-daratumumab (pooled ORR 64.5%), Pom-LoDex-cyclophosphamide (pooled ORR 59.4%, mean PFS 9.5 mos), Pom-LoDex-doxorubicin (pooled ORR 32%). Most frequently reported adverse event with Pom based regimens was myelosuppression. Mean incidences of grade ≥3 hematologic adverse events were neutropenia (47.6%), anemia (26.5%), and thrombocytopenia (20.8%). Mean incidences of grade ≥3 non-hematologic adverse events were infections (29.1%), pneumonia (13.8%) and fatigue (10%). Most of the studies used pomalidomide 4mg daily dosing. Lacy et al. suggested no advantage of 4mg pomalidomide over 2 mg daily dosing. Conclusion From results of pooled analysis, we can infer that triplet combinations of Pom yield almost double response rates (pooled ORR 61.9%) when compared to dual combination of Pom-LoDex (pooled ORR 35.7%). Among three drug combinations, Bort-Pom-LoDex (pooled ORR 83.5%) and CFZ-Pom-LoDex (pooled ORR 77.1%) seem to produce better outcomes. Our study provides useful insight into relative efficacy of various Pom regimens for treatment of RRMM patients. Several trials involving various MoAbs like nivolumab, daratumumab, elotuzumab, isatuximab and pembrolizumab in combination with Pom-LoDex are currently ongoing. Pomalidomide has an acceptable safety profile. Most common treatment emergent adverse events were myelotoxicity and infections that can be effectively managed with supportive care and dose modifications. Disclosures No relevant conflicts of interest to declare.

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