Abstract
The therapeutic human CD38 antibody daratumumab improves the anti-myeloma effect of newly emerging multi-drug therapies
Highlights
Multiple myeloma (MM) is an incurable malignancy of antibody-producing clonal plasma cells
With this ex vivo assay system, we first addressed the benefits of combining DARA with both LEN and BORT, since LEN and BORT may enhance the therapeutic efficacy of DARA by sensitizing tumor cells for antibody-mediated lysis
The highest MM cell lysis was observed with the triple LEN-BORT-DARA combination
Summary
Blood Cancer Journal (2011) 1, e41; doi:10.1038/bcj.2011.42; published online 28 October 2011. We explored the potential clinical benefit of combining targeted DARA therapy with newly emerging multi-drug chemotherapy regimens To this end, we used a recently developed ex vivo flow cytometry-based assay platform, which enables us to enumerate and subsequently deduce the drug/antibody-mediated lysis of primary CD138 þ MM cells directly in bone marrow samples from the MM patients. We have only been able to evaluate a small number of samples from resistant patients to date, this remarkable synergy suggests the maintenance of antitumorigenic properties of LEN and BORT, despite the development of drug resistance Taken together, these results indicate the potential clinical benefits of combining DARA with these two novel anti-MM agents and warrant further investigation even in patients who are low responders or have become resistant to the latter drugs. Addition of DARA to both RDV and MPV significantly increased the treatment efficacy by almost doubling the lysis levels p
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