[HTML][HTML] Atacicept in relapsed/refractory multiple myeloma or active Waldenström's macroglobulinemia: a phase I study

JF Rossi, J Moreaux, D Hose, G Requirand… - British Journal of …, 2009 - nature.com
JF Rossi, J Moreaux, D Hose, G Requirand, M Rose, V Rouille, I Nestorov, G Mordenti…
British Journal of Cancer, 2009nature.com
Background: Advanced multiple myeloma (MM) and Waldenström'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) …
Abstract
Background:
Advanced multiple myeloma (MM) and Waldenström'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.
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