POSTER 22
ADDITION OF DARATUMUMAB TO MULTIPLE MYELOMA BACKBONE REGIMENS
SIGNIFICANTLY IMPROVE CLINICAL OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS
OF RANDOMIZED CONTROLLED TRIALS
Szabolcs Kiss1,2, Noémi Gede2, Péter Hegyi2,3,4, Bettina Nagy2, Rita Deák2, Fanni Dembrovszky2, Stefania
Bunduc2, Tamás Leiner2,5, Bálint Erőss2,3,4, Zsolt Szakács2,4 and Hussain Alizadeh1,2,6
(1)Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
(2)Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
(3)János Szentágothai Research Centre, University of Pécs, Pécs, Hungary
(4)First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
(5)North West Anglia NHS Foundation Trust, Huntingdon, United Kingdom
(6)Division of Haematology, First Department of Medicine, Medical School, University of Pécs, Pécs,
Hungary
Objectives: Daratumumab is a CD38-targeted human IgG monoclonal antibody which has shown
promising clinical efficacy in multiple myeloma (MM). A systematic review and meta-analysis was
carried out to evaluate the effect of adding daratumumab to backbone anti-myeloma treatments on
therapeutic response and survival.
Methods: Systematic search was performed from inception to 14th October 2020 in Embase, MEDLINE,
CENTRAL, Scopus, and Web of Science to identify randomized controlled trials (RCT) comparing
backbone therapies with and without daratumumab in relapsed/refractory (RRMM) and newly
diagnosed (NDMM) patients. The primary outcomes were odds ratio (OR) for death or disease
progression, minimal residual disease (MRD) negativity and stringent complete response (sCR). Trial
Sequential Analysis (TSA) was performed for each outcome to quantify the statistical reliability and to
estimate the optimal information size (OIS). The study protocol was registered in PROSPERO
(CRD42020157338).
Results: Nine eligible articles reported on six daratumumab containing regimens and comprised
altogether 4268 patients. In the NDMM population, patients receiving daratumumab were more likely
to achieve MRD negativity OR=3.61 (95% CI: 2.33–5.61), I2=76.7% and sCR OR=2.29 (95% CI: 1.49–
3.51) I2=77.5%. For MRD negativity and sCR, quantitative synthesis could not be carried out in RRMM
population. Death or disease progression was less likely to occur in the daratumumab group in NDMM
OR=0.47 (95% CI: 0.39–0.57), I2=28.5% and RRMM OR=0.53 (95% CI: 0.38–0.75), I2=62.9% as well.
For this outcome, subgroup analyses could also be carried out among standard OR=0.43 (95% CI: 0.35–
0.53), I2=0.0% and high cytogenetic risk patients OR=0.78 (95% CI: 0.53–1.10), I2=0.0% in NDMM.
Based on our analyses, OIS was reached for each outcome, except for the subgroup analysis in the high
cytogenetic risk NDMM population.
Conclusion: Our results support the incorporation of daratumumab in backbone therapies in MM;
however additional studies are needed to further specify the population that gains the most benefits
from this treatment, especially in high cytogenetic risk NDMM, where the OIS was not reached.