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Antibody Based Three-Drug Regimens for Multiple Myeloma - a Systematic Review of Phase II and Phase III Clinical Trials
Introduction Elotuzumab is monoclonal antibody (mAb) that specifically targets signaling lymphocytic activation molecule family member 7 (SLAMF7) that is present on myeloma cells. It fights myeloma cells by stimulating phagocytic action of NK cells and via ADCC (antibody‐dependent cell‐mediated cyto...
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| Published in: | Blood 2019-11, Vol.134 (Supplement_1), p.5546-5546 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Online Access: | Get full text |
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| Summary: | Introduction
Elotuzumab is monoclonal antibody (mAb) that specifically targets signaling lymphocytic activation molecule family member 7 (SLAMF7) that is present on myeloma cells. It fights myeloma cells by stimulating phagocytic action of NK cells and via ADCC (antibody‐dependent cell‐mediated cytotoxicity) pathway. Daratumumab is an anti-CD38 mAb with dual mechanisms of action i.e. tumoricidal and immunomodulation. The aim of this study is to review the efficacy and toxicity of elotuzumab and daratumumab based 3-drug combinations in patients (pts) with multiple myeloma (MM).
Methods
A systematic search of PubMed, Embase, Clinicaltrials.gov, Cochrane and Web of Science was performed for elotuzumab and daratumumab based regimen in MM patients from inception to June 12, 2019. Out of 604 studies, 08 phase II and III clinical trials based on 3-drug regimen were finalized.
Results
Total 2809 patients (pts) were evaluated out of 2879 enrolled pts. 856 were newly diagnosed (ND) and 1953 were relapsed/refractory (R/R). Elotuzumab (E) based 3-drug regimen were evaluated in 560 whereas daratumumab (D) based 3-drug regimen were analyzed in 889 pts.
ELOQUENT-3 trial (n=117) in phase II used E + pomalidomide (P) and dexamethasone (d) (EPd) for R/R pts with ≥2 prior therapies. Median (m) progression free survival (PFS) was 10.2 months (mo) in EPd versus (vs) 4.6 mo in Pd arm [Hazard ratio (HR) 0.54 (95% CI: 0.34-0.86; p=0.008)], i.e. 46% lower risk of progression or death in EPd vs Pd arm. ORR (overall response rate) was 53% (complete response [CR] 5% + stringent CR [sCR] 3% + partial response [PR] 33% + very good partial response [VGPR] 12%) in EPd vs 26% in Pd arm (odds ratio [OR]: 3.25 (1.49-7.11). Grade (G) ≥3 adverse events (AEs) were anemia (10%), neutropenia and infections (13% each). (Dimopoulos et al. 2018).
Phase II trial by Jakubowiak et al. (2016) observed 1 year (y) PFS of 39% in E-Bortezomib(B)-d vs 33% in Bd arm in 152 R/R pts (HR: 0.72; p = .09) with 28% decrease in progression or death with EBd vs Bd. ORR was 66% (4% CR+ 33% VGPR + 30% PR) vs 63%. OS (overall survival) at 1 y was 85% (EBd) and 74% (Bd) (HR:0.6). G≥3 AEs were infections (21%), thrombocytopenia and peripheral neuropathy (9% each). In phase II trial, ELd (E-Lenalidomide-d) arm yielded ORR of 88% (CR 3% + sCR 5% + PR 43% + VGPR 38%) vs 74% in Ld arm in 82 ND pts. PFS at 1 yr was 93% vs 91%. G≥3 AEs included neutropenia (18%) and leukopenia (15%). (Takezako et al. 2017). Berenson et al. (20 |
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| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood-2019-121999 |