Genmab — November 2017
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the ID combination significantly enhanced mitochondrial-mediated apoptosis in both CD38hi and CD38lo cells. This indicates that the combination can potentially overcome lower induction of apoptosis and ADCC in CD38lo cells treated with single agent Dara or Ibr. Studies on how Dara and the ID combination induce direct programmed cell death (independent of modulating BCR signaling) are underway. Overall, our investigations provide rationale for clinical testing of Ibr combined with Dara in CLL.
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in the era of BCR kinase inhibitors, daratumumab immunotherapy opens a new horizon offering unique effects on tumor dissemination against CD38+ CLL cases. In conclusion, our results support daratumumab as a novel therapeutic approach for CD38+ CLL by not only inducing the classical FcγR-mediated cytotoxicity but also harnessing microenvironment-derived survival signaling and blocking CLL dissemination to secondary lymphoid organs.
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