Phase I study of atacicept in relapsed/refractory multiple myeloma (MM) and Waldenström's macroglobulinemia.

Atacicept, a specific inhibitor of BLys and APRIL, was used in a phase I study for 14 patients with myeloma (MM) and 4 with Waldenström's macroglobulinemia (WM). They received 1 cycle of 5 once-weekly s.c. injections, followed by an extension if in stable disease or in response. The maximum tolerated dose was not identified. Of 11 patients with MM who completed initial treatment, 5 patients were progression-free after cycle 1 and 4 patients were progression-free after extended therapy. Of 4 patients with WM, 3 patients were progression-free after cycle 1. Polyclonal immunoglobulin isotypes and total B cells were reduced. Plasma concentrations of soluble CD 138 decreased. Biological effect was more pronounced in WM. Of the 16 patients tested at baseline, 13 had measurable levels of free APRIL (≥25 ng/mL). In this small series, no correlations were apparent between baseline levels of free APRIL and biological or clinical response criteria.