Atacicept in relapsed/refractory multiple myeloma or active Waldenstrom's macroglobulinemia: a phase I study

BACKGROUND: Advanced multiple myeloma ( MM) and Waldenstrom's macroglobulinemia (WM) are incurable B-cell malignancies. This is the first full clinical report of atacicept, a fusion protein that binds to and neutralises the B-cell survival factors, B-lymphocyte stimulator ( BLyS) and A proliferation-inducing ligand (APRIL), in MM and WM. METHODS: In this open-label phase-I study, 16 patients with advanced disease ( 12 MM, 4 WM) received one cycle of five once-weekly subcutaneous injections of atacicept (2, 4, 7 or 10 mg kg(-1)). Patients with stable disease after cycle 1 entered an extension study ( either two additional cycles ( 2, 4 and 7 mg kg(-1) cohorts) or 15 consecutive weekly injections of atacicept 10 mg kg(-1)). RESULTS: Atacicept was well tolerated, systemically and locally; the maximum tolerated dose was not identified. Of 11 patients with MM who completed initial treatment, five patients were progression-free after cycle 1 and four patients were progression-free after extended therapy. Of four patients with WM, three patients were progression-free after cycle 1. Consistent with atacicept's mechanism of action, polyclonal immunoglobulin isotypes and total B cells were reduced. Bone-marrow density, myeloma cell numbers and plasma concentrations of soluble CD138 also decreased. CONCLUSION: Atacicept is well tolerated in patients with MM and WM, and shows clinical and biological activity consistent with its mechanism of action. British Journal of Cancer (2009) 101, 1051-1058. doi:10.1038/sj.bjc.6605241 www.bjcancer.com (C) 2009 Cancer Research UK