Oncotarget

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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

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

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Oncotarget. 2017; 8:34001-34017. https://doi.org/10.18632/oncotarget.16987

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Abstract

Tiantian Zhang1,*, Sen Wang1,*, Tengfei Lin2, Jingmei Xie1, Lina Zhao1, Zhuoru Liang1, Yangqiu Li3,4 and Jie Jiang1,5

1 College of Pharmacy, Jinan University, Guangzhou 510632, People’s Republic of China

2 College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, People’s Republic of China

3 Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou 510632, People’s Republic of China

4 Institute of Hematology, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China

5 Institute of Dongguan, Jinan University, Dongguan 523808, People’s Republic of China

* These authors have contributed equally to this work

Correspondence to:

Jie Jiang, email:

Keywords: monoclonal antibody, elotuzumab, daratumumab, relapsed or refractory, multiple myeloma

Received: November 23, 2016 Accepted: March 11, 2017 Published: April 09, 2017

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.


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