CD38 and CD45 expression on plasma cells and response to daratumumab in Multiple Myeloma

Background
Studies that evaluated the relationship between CD38 expression on plasma cells and response to daratumumab in multiple myeloma patients show conflicting results Whereas Nijhof et al. found a significantly higher CD38 expression in responders compared to non-responders, Pick et al. found no difference between these two groups. In addition, although Nijhof et al. showed a decrease in CD38 expression 14 weeks after start of treatment with daratumumab, CD38 expression was partly regained after 6 months. Case reports also describe this phenomenon, however the known interference of daratumumab with diagnostic CD38 antibodies in flow cytometry creates the need for these results to be approached with caution. Fc-receptor-mediated cross-linking induced apoptosis is a newly discovered mechanism of action of daratumumab. Kimlinger et al. found that CD45+ multiple myeloma cells show higher apoptotic rates, therefore we hypothesized that higher CD45 expression is associated with better response to daratumumab. The primary aim of this study is thus to compare CD38 expression before and after treatment between responders and non-responders to treatment with daratumumab, given as monotherapy or as combination treatment. The secondary aim is to compare CD45 expression between these groups.

Methods
In flow cytometry experiments, cells from bone marrow samples of relapsed myeloma patients were stained with CD38, CD138, CD45, CD56, CD19, and cytoplasmic kappa/lambda, as described by Nijhof et al. and Krejcik et al. Total plasma cells were defined as CD38+/CD138+ cells. Monoclonal plasma cells were gated as CD19- /CD56+ or CD56- and solely expressing either lambda or kappa light chains. Patient characteristics, including response evaluation - (at least PR or less than PR) - and progression-free survival, were retrieved from medical records. Mann-Whitney U tests were performed to compare median fluorescence intensity (median [IQR]) between groups. Preliminary results A total of 32 multiple myeloma patients were analyzed for CD38 and CD45 expression before start of daratumumab treatment. Results show that the CD38 expression in monoclonal plasma cells is higher in responders compared to non-responders (12963 [9913.5, 31016] vs. 11924 [6495, 15304]) (p = 0.266). In contrast, CD45 expression was lower in responders compared to non-responders (630.5 [528, 842.25] vs. 710 [590, 1051]) (p = 0.427).

Conclusion
Our preliminary results show a higher CD38 expression in patients that had a better response to daratumumab. CD45 seems not to play a role in daratumumab-mediated cell killing. Our results did not reach statistical significance due to the limited number of samples evaluated so far. Data from 15 or more patients will be included in the study in order to validate our findings. Understanding more about CD38 expression before and after treatment with daratumumab provides important information that guides clinicians in their choice of therapy.