Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma.
Клиническое исследование I фазыСтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Topp Max S, Duell Johannes, Zugmaier Gerhard, Attal Michel, Moreau Philippe, Langer Christian, Krönke Jan, Facon Thierry, Salnikov Alexey V, Lesley Robin, Beutner Karl, Kalabus James, Rasmussen Erik, Riemann Kathrin, Minella Alex C, Munzert Gerd, Einsele Hermann
Аннотация
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 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.
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 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.