Protein Expression Linked With Daratumumab Resistance for Multiple Myeloma Patients

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Therapies that alter expression of the CD-38 glycoprotein and complement-inhibitory proteins (CIPs) should be studied in the treatment of multiple myeloma.
Therapies that alter expression of the CD-38 glycoprotein and complement-inhibitory proteins (CIPs) should be studied in the treatment of multiple myeloma.

Therapies that alter expression of the CD-38 glycoprotein and complement-inhibitory proteins (CIPs) should be studied in the treatment of multiple myeloma, according to a study published in Blood.1

Daratumumab, an anti-CD38 monoclonal antibody, is often clinically beneficial for pretreated patients with relapsed or refractory multiple myeloma. Responses, however, are not consistent, and many patients develop resistance.

Researchers enrolled 102 patients receiving 16mg/kg daratumumab monotherapy, and found that pretreatment CD38 expression on myeloma cells was higher in patients who tended to respond to the drug. Expression of CIPs--membrane cofactor protein (CD46), decay‐accelerating factor (CD55), and protectin (CD59)--was not associated with clinical response.

Following therapy discontinuation, CD38 expression on myeloma cells increased, whereas CD55 and CD59 levels increased on myeloma cells only at disease progression.

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It was concluded both that daratumumab is associated with CD38 expression level on myeloma cells, and that CD38-targeting antibody resistance is positively correlated with expression of CIPs. More research, the authors suggest, is needed to show the significance of CD38 and CIP expression levels in multiple myeloma treatment.

Reference

  1. Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, et al. CD38 levels are associated with response and complement inhibitors contribute to resistance in myeloma patients treated with daratumumab. Blood. doi: 10.1182/blood-2016-03-703439.

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