Anti–B-cell maturation antigen bite molecule AMG 420 induces responses in multiple myeloma

Topp MS, Duell J, Zugmaier G, Attal M, Moreau P, Langer C, Kroenke J, Facon T, Salnikov AV, Lesley R, Beutner K, Kalabus J, Rasmussen E, Riemann K, Minella AC, Munzert G, Einsele H (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Journal of Clinical Oncology American Society of Clinical Oncology

Book Volume: 38

Pages Range: 775-783

Journal Issue: 8

DOI: 10.1200/JCO.19.02657

Abstract

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/104 bone marrow cells by flow cytometry. RESULTS Forty-two patients received AMG 420 at 0.2-800 mg/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 mg/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 mg/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 mg/d, the MTD for this study.

Involved external institutions

Amgen Inc. US United States (USA) (US) Universitätsklinikum Würzburg DE Germany (DE) Amgen GmbH DE Germany (DE) Université Fédérale de Toulouse Midi-Pyrénées FR France (FR) Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU) FR France (FR) Klinikum Kempten DE Germany (DE) Universität Ulm DE Germany (DE) Boehringer Ingelheim Pharma GmbH & Co. KG DE Germany (DE) Centre Hospitalier Régional Universitaire de Lille (CHRU de Lille) FR France (FR)

How to cite

APA:

Topp, M.S., Duell, J., Zugmaier, G., Attal, M., Moreau, P., Langer, C.,... Einsele, H. (2020). Anti–B-cell maturation antigen bite molecule AMG 420 induces responses in multiple myeloma. Journal of Clinical Oncology, 38(8), 775-783. https://doi.org/10.1200/JCO.19.02657

MLA:

Topp, Max S., et al. "Anti–B-cell maturation antigen bite molecule AMG 420 induces responses in multiple myeloma." Journal of Clinical Oncology 38.8 (2020): 775-783.

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