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Updated: Jun 3, 2026
Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube (SWCNT)-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
Phase I study of atacicept in relapsed/refractory multiple myeloma (MM) and Waldenström's macroglobulinemia
1Department of Haematology, University Hospital, CHU Saint Eloi, Montpellier, France. jf-rossi@chu-montpellier.fr
Abstract:
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.
Insights
Atacicept, a B-cell therapy, showed promise in a phase I trial for myeloma and Waldenström's macroglobulinemia patients, with some achieving disease stabilization. Further research is warranted to explore its full potential.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL) are key cytokines in B-cell survival and proliferation.
- Aberrant BAFF/APRIL signaling contributes to the pathogenesis of B-cell malignancies like multiple myeloma (MM) and Waldenström's macroglobulinemia (WM).
Purpose of the Study:
- To evaluate the safety, tolerability, and preliminary efficacy of atacicept, a dual inhibitor of BAFF and APRIL, in patients with relapsed or refractory MM and WM.
- To assess the biological effects of atacicept, including changes in B-cell populations and immunoglobulin levels.
Main Methods:
- A phase I, open-label, dose-escalation study of atacicept administered subcutaneously once weekly for 5 weeks.
- Patients with MM (n=14) and WM (n=4) were enrolled. Treatment could be extended for patients with stable disease or response.
- Safety assessments, including adverse events and maximum tolerated dose (MTD), were performed. Efficacy was evaluated by progression-free survival (PFS). Biological markers such as B-cell counts, immunoglobulin levels, and soluble CD138 were measured.
Main Results:
- The MTD was not reached. Atacicept was generally well-tolerated.
- In MM patients (n=11) completing initial treatment, 5 remained progression-free after cycle 1, and 4 after extended therapy.
- In WM patients (n=4), 3 were progression-free after cycle 1.
- Significant reductions in polyclonal immunoglobulin isotypes, total B cells, and plasma soluble CD138 were observed.
- Biological effects were more pronounced in WM patients.
Conclusions:
- Atacicept demonstrated preliminary activity and was well-tolerated in patients with MM and WM.
- The drug induced significant B-cell depletion and reduction in key biomarkers.
- Further investigation in larger trials is warranted to confirm efficacy and optimize treatment strategies for these hematologic malignancies.
