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

Tiantian Zhang, Sen Wang, Tengfei Lin, Jingmei Xie, Lina Zhao, Zhuoru Liang, Yangqiu Li, Jie Jiang, Tiantian Zhang, Sen Wang, Tengfei Lin, Jingmei Xie, Lina Zhao, Zhuoru Liang, Yangqiu Li, Jie Jiang

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.

Keywords: daratumumab; elotuzumab; monoclonal antibody; multiple myeloma; relapsed or refractory.

Conflict of interest statement

CONFLICTS OF INTEREST

We are indebted to no conflicts of interest with anyone.

Figures

Figure 1. Identification and selection of the…
Figure 1. Identification and selection of the studies included in the meta-analysis
Figure 2. Meta-analysis of the efficacy of…
Figure 2. Meta-analysis of the efficacy of mAbs-based regimens in patients with RRMM: (A) overall response rate of mAbs-based single, doublet and triplet regimens;(B) at least very good partial response of mAb-based single, doublet and triplet regimens;(C) odds ratio of overall response of mAb-based triplet compared with controlled arm; (D) odds ratio of at least very good partial response of mAbs-based triplet compared with controlled arm;(E) hazard ratios for progression free survival of mAbs-based triplet compared with controlled arm
ORR, overall response rate; VGPR, very good partial response; OR, odds ratio; HR, hazard ratio; CI, confidence interval
Figure 3. Meta-analysis of the efficacy of…
Figure 3. Meta-analysis of the efficacy of elotuzumab-based regimens in patients with RRMM: (A) overall response rate of elotuzuamb-based single, doublet and triplet regimens; (B) at least very good partial response of elotuzumab-based single, doublet and triplet regimens
ORR, overall response rate; VGPR, very good partial response; CI, confidence interval. Etriplet, elotuzumab-based triplet regimen; Edoublet, elotuzumab-based doublet regimen; Esingle, elotuzumab-based single regimen
Figure 4. Meta-analysis of the efficacy of…
Figure 4. Meta-analysis of the efficacy of daratumumab-based regimens in patients with RRMM:(A) overall response rate of daratumumab-based single and triplet regimens;(B) at least very good partial response of daratumumab-based single and triplet regimens;(C) overall response rate of daratumumab-based monotherapy (16mg/kg);(D) at least very good partial response of daratumumab-based monotherapy (16mg/kg)
ORR, overall response rate; VGPR, very good partial response;CI, confidence interval.Dtriplet, daratumumab-based triplet regimen; Dsingle, daratumumab-based single regimen.
Figure 5. Meta-analysis of the IRRs of…
Figure 5. Meta-analysis of the IRRs of mAbs-based regimens in patients with RRMM: (A) any grade infusion-related reactions rate of mAbs;(B) the rate of IRR occurs in first time infusion; (C) grade 3 infusion-related reactions rate of mAbs;(D) the rate of discontinue due to IRRs
IRR, infusion related reactions; CI, confidence interval; E: elotuzumab; D: daratumumab
Figure 6. Leave-one-out analysis of the efficacy…
Figure 6. Leave-one-out analysis of the efficacy of daratumumab and elotuzumab-based triplet regimens in patients with RRMM: (A) overall response rate of elotuzumab-based triplet regimens;(B) at least very good partial response of elotuzumab-based triplet regimens;(C) overall response rate of daratumumab-based triplet regimens;(D) at least very good partial response of daratumumab-based triplet regimens
CI, confidence interval.

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