Résumé
In newly diagnosed as well as in relapsed/refractory multiple myeloma, the anti CD38 monoclonal antibody daratumumab (dara) has become essential in the therapeutic arsenal. Up to now, very few predictive factors of response to dara have been identified in clinical studies. Even low expression of CD38 appears controversial. We retrospectively collected clinical and biological data from 97 patients treated with dara at first line or at relapse at Montpellier University Hospital between 2016 and 2020. Biological data included multiparameter flow cytometry (MFC) phenotype of plasma cells, cytogenetic data and transcriptomic gene expression profiling (GEP) data. We collected the expression of plasma cell markers CD200, CD117, CD56, CD38, CD45 and CD27 on tumor plasma cells before treatment with dara.The objective of this study was to look for predictive factors of response to Dara looking in an unbiased approach at clinical and biological parameters.Multivariate logistic regression confirmed that the use of dara in combination with other molecules (p=0.044, OR 4.4, 95% CI 1.1-20.7) especially iMiDs and in first line (p=0.042, OR 11.4, 95% CI 1.5-245.2) allows to obtain better response to treatment.Maxstat analysis found that high CD200 expression (≥ 95%) was significantly associated with poorer progression free survival (PFS) (p=0.02), whereas high CD56 expression (≥95%) and CD45 expression ≥50% were significantly associated with better PFS (p=0.01 for CD45 and p=0.03 for CD56). High CD56 expression was also correlated with better response to dara in multivariate logistic regression (p=0.002, OR 9.9 95% CI 2.6-48.5). GEP complementary analysis found a significant enrichment in inflammatory response genes, genes encoding extracellular matrix and in PRC2 polycomb target genes in responders to dara. In this series of 97 patients, very well documented both clinically and biologically, we were able to identify new markers of response to Dara: high expression of CD56, PRC2 target genes and high inflammatory and extracellular matrix gene expression. This study is the first to identify phenotypic and molecular factors predictor of response to dara.