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


CONCLUSIONS
Atacicept is well tolerated in patients with MM and WM, and shows clinical and biological activity consistent with its mechanism of action.
Rossi
J-F
JF
CIC-Biothérapie BT 509, CHU Montpellier, Montpellier, France. jf-rossi@chu-montpellier.fr
Moreaux
J
J
Hose
D
D
Requirand
G
G
Rose
M
M
Rouillé
V
V
Nestorov
I
I
Mordenti
G
G
Goldschmidt
H
H
Ythier
A
A
Klein
B
B
D000368:Aged; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053668:Syndecan-1 / Q000097:blood; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011993:Recombinant Fusion Proteins; C508241:SDC1 protein, human; D053668:Syndecan-1; C524618:TACI receptor-IgG Fc fragment fusion protein