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Systematic review and meta-analysis of the efficacy and safety of novel monoclonal antibodies for treatment of relapsed/refractory multiple myeloma.

ABSTRACT: Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma (RRMM), their efficacy and safety remain uncertain. We therefore performed a systematic review and meta-analysis of the most recent clinical trials that evaluated elotuzumab and/or daratumumab for the treatment of patients with RRMM. Our meta-analysis included 13 clinical trials with 2,402 patients participating. The overall response rate (ORR) was 57% (95% confidence interval [CI]: 38-76%), and the at least very good partial response rate (VGPR) was 32% (95% CI: 19-46%). mAb-based regimens prolonged progression-free survival (PFS, hazard ratio: 0.52, 95% CI: 0.36-0.75) compared to non-mAb-based regimens. Additionally, the efficacy of triplet regimens was superior to that of single or doublet regimens. The same trend was observed in a subgroup analysis of daratumumab and elotuzumab. The most common grade 3/4 adverse events included neutropenia, lymphopenia, thrombocytopenia, anemia, leukopenia, pneumonia, and fatigue. Elotuzumab and daratumumab improved the ORR, at least VGPR, and PFS compared to non-mAb-based regimens. In a pooled analysis, both mAbs had promising efficacy and safety profiles, particularly in triplet regimens. The same trend was observed in daratumumab- and elotuzumab-based regimens. Daratumumab triplet therapy (daratumumab, lenalidomide, and dexamethasone) was superior to other triplet regimens for the treatment of RRMM, and daratumumab monotherapy was more effective than either single agent in heavily pretreated MM patients, suggesting CD38 is an effective target for treatment of RRMM. Additional clinical studies of elotuzumab and daratumumab will be required to validate these results.

SUBMITTER: Zhang T

PROVIDER: S-EPMC5464929 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Systematic review and meta-analysis of the efficacy and safety of novel monoclonal antibodies for treatment of relapsed/refractory multiple myeloma.

Zhang Tiantian T Wang Sen S Lin Tengfei T Xie Jingmei J Zhao Lina L Liang Zhuoru Z Li Yangqiu Y Jiang Jie J

Oncotarget 20170501 20

Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma (RRMM), their efficacy and safety remain uncertain. We therefore performed a systematic review and meta-analysis of the most recent clinical trials that evaluated elotuzumab and/or daratumumab for the treatment of patients with RRMM. Our meta-analysis included 13 clinical trials with 2,402 patients participating. The overall respon ...[more]

PMID: 28454113

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Project description:ObjectivesTo systematically review and meta-analyse the evidence for effect modification by refractory status and number of treatment lines in relapsed/refractory multiple myeloma (RRMM); and to assess whether effect modification is likely to invalidate network meta-analyses (NMA) that assume negligible modification.DesignSystematic review, meta-analysis and simulation.Data sourcesWe systematically searched the literature (e.g., OVID Medline) to identify eligible publications in February 2020 and regularly updated the search until January 2022. We also contacted project stakeholders (including industry) ELIGIBILITY CRITERIA: Phase 2 and 3 randomised controlled trials reporting stratified estimates for comparisons with at least one of a prespecified set of treatments relevant for use in Norwegian RRMM patients.OutcomesWe used meta-analysis to estimate relative HRs (RHRs) for overall survival (OS) and progression-free survival (PFS) with respect to refractory status and number of treatment lines. We used the estimated RHRs in simulations to estimate the percentage of NMA results expected to differ significantly in the presence versus absence of effect modification.ResultsAmong the 42 included publications, stratified estimates were published by and extracted from up to 18 (43%) publications and on as many as 8364 patients. Within-study evidence for effect modification is very weak (p>0.05 for 47 of 49 sets of stratified estimates). The largest RHR estimated was 1.32 (95% CI 1.18 to 1.49) for the modifying effect of refractory status on HR for PFS. Simulations suggest that, in the worst case, this would result in only 4.48% (95% CI 4.42% to 4.54%) of NMA estimates differing statistically significantly in the presence versus absence of effect modification.ConclusionsBased on the available evidence, effect modification appears to be sufficiently small that it can be neglected in adequately performed NMAs. NMAs can probably be relied on to provide estimates of HRs for OS and PFS in RRMM, subject to caveats discussed herein.

Project description:Background: Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. Methods: To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clinical trials from PUBMED, EMBASE, and The Cochrane Library. For safety analysis, the incidence and exhibition of any grade and grade ?3 adverse events (AEs) were evaluated. Overall response rate (ORR), 6-month progression-free survival (PFS) and 6-month overall survival (OS) were calculated for efficacy analysis. Results: Overall ten studies and 718 patients (114 non-Hodgkin lymphomas, 604 Hodgkin lymphomas) were enrolled, including 4 phase I studies and 6 phase II studies. The pooled incidences of any grade and grade ?3 adverse events (AEs) were 74 and 24%, respectively. Drug-related deaths occurred in two patients. The most common any grade AEs were fatigue (14.91%), rash (14.8%), hypothyroidism (13.77%), platelet count decreased (13.54%), pyrexia (13%). The most common grade ?3 AEs were neutropenia (4.79%), pneumonitis (3.58%), rash (3.38%), and leukopenia (3.31%). Fatigue (p = 0.0072) and rash (p = 0.0078) in any grade AEs were less observed in patients treated with pembrolizumab than nivolumab. The pooled ORR, PFS rate and OS rate were 58, 73, and 96%, respectively. The ORR in patients with Hodgkin lymphomas (HL) was higher than patients with non-Hodgkin lymphomas (NHL) (69.08 vs. 30.77%, p < 0.0001). However, there was no significant difference of efficacy between nivolumab and pembrolizumab. Conclusions: Nivolumab and pembrolizumab have promising outcomes with tolerable AEs and drug-related deaths in patients with relapsed or refractory lymphoma. Pembrolizumab caused less any grade AEs like fatigue and rash than nivolumab. Patients with HL got better response than NHL.

Dataset Information

Systematic review and meta-analysis of the efficacy and safety of novel monoclonal antibodies for treatment of relapsed/refractory multiple myeloma.

Publications

Systematic review and meta-analysis of the efficacy and safety of novel monoclonal antibodies for treatment of relapsed/refractory multiple myeloma.

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