Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Siltuximab in High-Risk Smoldering Multiple Myeloma
Por:
Brighton, TA, Khot, A, Harrison, SJ, Ghez, D, Weiss, BM, Kirsch, A, Magen, H, Gironella, M, Oriol, A, Streetly, M, Kranenburg, B, Qin, X, Bandekar, R, Hu, P, Guilfoyle, M, Qi, M, Nemat, S and Goldschmidt, H
Publicada:
1 jul 2019
Ahead of Print:
19 mar 2019
Resumen:
Purpose: IL6 is important for the growth and survival of myeloma cells. This study evaluated blocking IL6 with siltuximab to delay the transition from high-risk smoldering multiple myeloma (SMM) to multiple myeloma.
Patients and Methods: In a randomized, double-lind, placebo-controlled, multicenter study, 85 patients with high-risk SMM were randomized to 15 mg/kg siltuximab (43 patients) or placebo (42 patients). The primary endpoint was 1-year progression-free survival (PFS) rate, based on IMWG CRAB criteria. Secondary endpoints included progressive disease indicator rate, PFS, and safety.
Results: Median age was 62 years (range: 21-84); 57% were male and 87% had a baseline Eastern Cooperative Oncology Group score of 0. The 1-year PFS rate was 84.5% (siltuximab) and 74.4% (placebo). After a median followup of 29.2 months, 32.6% of PFS events occurred with siltuximab and 42.9% with placebo. Median PFS was not reached with siltuximab but was 23.5 months with placebo [HR 0.50 (95% confidence interval, 0.24-.04); P = 0.0597]. The safety profile of siltuximab was comparable with placebo. Most adverse events in the siltuximab group were grade 2/3; the most common serious adverse events were infections/infestations, and renal/urinary disorders. Mortality was low in both groups (3 deaths in the siltuximab group and 4 in the placebo group).
Conclusions: Although this study did not meet the prespecified protocol hypothesis criteria, data suggest that siltuximab may delay the progression of high-risk SMM.
Filiaciones:
Brighton, TA:
Prince Wales Hosp, Randwick, NSW, Australia
Khot, A:
Peter MacCallum Canc Ctr, Clin Haematol, Melbourne, Vic, Australia
Royal Melbourne Hosp, Melbourne, Vic, Australia
Harrison, SJ:
Peter MacCallum Canc Ctr, Clin Haematol, Melbourne, Vic, Australia
Royal Melbourne Hosp, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
Ghez, D:
Serv Hematol, Dept Med, Gustave Roussy Canc Campus, Villejuif, France
Weiss, BM:
Univ Penn, Dept Med, Div Hematol Oncol, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA
Kirsch, A:
Med Versorgungszentrum Onkol Schwerpunkt Oskar He, Berlin, Germany
Magen, H:
Beilinson Med Ctr, Rabin Med Ctr, Davidoff Canc Ctr, Inst Hematol, Petah Tiqwa, Israel
Gironella, M:
Hosp Univ Vall Dhebron, Haematol Dept, Barcelona, Spain
:
Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Inst Josep Carreras, Barcelona, Spain
Streetly, M:
Guys & St Thomas NHS Fdn Trust, Guys Hosp, Clin Haematol, London, England
Kranenburg, B:
Janssen Biol BV, Leiden, Netherlands
Qin, X:
Janssen Res & Dev LLC, Spring House, PA USA
Bandekar, R:
Janssen Res & Dev LLC, Spring House, PA USA
Hu, P:
Janssen Res & Dev LLC, Raritan, NJ USA
Guilfoyle, M:
Janssen Res & Dev LLC, Raritan, NJ USA
Qi, M:
Janssen Res & Dev LLC, Spring House, PA USA
Nemat, S:
Janssen Cilag Ltd, High Wycombe, Bucks, England
Goldschmidt, H:
Univ Hosp, Internal Med 5, Heidelberg, Germany
Natl Ctr Tumor Dis Heidelberg, Heidelberg, Germany
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