A multicenter phase II study of single-agent enzastaurin in previously treated multiple myeloma.

Enzastaurin is an oral serine/threonine kinase inhibitor of the protein kinase C (PKC) and phosphatidylinositol 3 (PI3) kinase/Akt pathways that induces apoptosis in multiple myeloma (MM) cell lines in a caspase-independent manner. A phase II study was conducted to assess response rate, time to progression (TTP), safety and biomarker association with clinical outcomes after monotherapy with the PKC inhibitor enzastaurin in previously treated patients with MM. Eligible patients (n = 14) were treated with enzastaurin 250 mg twice daily after receiving loading doses on day 1. One minimal response was observed. The median TTP was 5.11 months. There were two grade 3 adverse events, anemia and prolonged QTc interval, and no grade 4 adverse events. Single-agent enzastaurin was well tolerated but not effective in this heavily pretreated population with MM.