Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma.

Autor:	Topp MS; Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany., Duell J; Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany., Zugmaier G; Amgen Research (Munich), Munich, Germany., Attal M; University of Toulouse, Toulouse, France., Moreau P; Hematology Department, University Hospital Center of Nantes, Nantes, France., Langer C; Kempten Clinic, Kempten, Germany., Krönke J; Ulm University, Ulm, Germany., Facon T; Regional University Hospital of Lille, Lille, France., Salnikov AV; Boehringer Ingelheim, Biberach, Germany., Lesley R; Amgen, South San Francisco, CA., Beutner K; Amgen, Thousand Oaks, CA., Kalabus J; Amgen, South San Francisco, CA., Rasmussen E; Amgen, Thousand Oaks, CA., Riemann K; Boehringer Ingelheim, Biberach, Germany., Minella AC; Amgen, Thousand Oaks, CA., Munzert G; Boehringer Ingelheim, Biberach, Germany., Einsele H; Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Mar 10; Vol. 38 (8), pp. 775-783. Date of Electronic Publication: 2020 Jan 02.
DOI:	10.1200/JCO.19.02657
Abstrakt:	Purpose: The anti-B-cell maturation antigen BiTE molecule AMG 420 was assessed in patients with relapsed/refractory multiple myeloma. Patients and Methods: In this first-in-human study, up to 10 cycles of AMG 420 were given (4-week infusions/6-week cycles). Patients had progression after ≥ 2 lines of prior therapy and no extramedullary disease. Minimal residual disease (MRD) response was defined as < 1 tumor cell/10 4 bone marrow cells by flow cytometry. Results: Forty-two patients received AMG 420 at 0.2-800 μg/d. Median age was 65 years, and median disease duration was 5.2 years. Median exposure was 1 cycle (range, 1-10 cycles) and 7 cycles (range, 1-10 cycles) for responders. Patients discontinued for disease progression (n = 25), adverse events (AEs; n = 7), death (n = 4), completion of 10 cycles (n = 3), and consent withdrawal (n = 1). Two patients remain on treatment. There were 2 nontreatment-related deaths from AEs, influenza/aspergillosis and adenovirus-related hepatitis. Serious AEs (n = 20; 48%) included infections (n = 14) and polyneuropathy (n = 2); treatment-related serious AEs included 2 grade 3 polyneuropathies and 1 grade 3 edema. There were no grade ≥ 3 CNS toxicities or anti-AMG 420 antibodies. In this study, 800 μg/d was considered to not be tolerable because of 1 instance each of grade 3 cytokine release syndrome and grade 3 polyneuropathy, both of which resolved. The overall response rate was 31% (n = 13 of 42). At the maximum tolerated dose (MTD) of 400 μg/d, the response rate was 70% (n = 7 of 10). Of these, five patients experienced MRD-negative complete responses, and 1 had a partial response, and 1 had a very good partial response; all 7 patients responded during the first cycle, and some responses lasted > 1 year. Conclusion: In this study of AMG 420 in patients with relapsed/refractory multiple myeloma, the response rate was 70%, including 50% MRD-negative complete responses, at 400 μg/d, the MTD for this study.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu