Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
Por:
Moreau, P, Dimopoulos, MA, Mikhael, J, Yong, K, Capra, M, Facon, T, Hajek, R, Spicka, I, Baker, R, Kim, K, Martinez, G, Min, CK, Pour, L, Leleu, X, Oriol, A, Koh, Y, Suzuki, K, Risse, ML, Asset, G, Mace, S and Martin, T
Publicada:
19 jun 2021
Ahead of Print:
1 jun 2021
Resumen:
Background Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone for relapsed or refractory multiple myeloma. This phase 3, openlabel study compared the efficacy of isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple rnyeloma.
Methods This was a prospective, randomised, open-label, parallel-group, phase 3 study done at 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients with relapsed or refractory multiple rnyelorna aged at least 18 years who had received one to three previous lines of therapy and had measurable serum or urine M-protein were eligible. Patients were randomly assigned (3:2) to isatuximab plus carfilzomib-dexamethasone (isatuximab group) or carfilzomib-dexamethasone (control group). Patients in the isatuximab group received isatuximab 10 mg/kg intravenously weekly for the first 4 weeks, then every 2 weeks. Both groups received time approved schedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatment continued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assigned treatment. Safety was assessed in all patients who received at least one dose according to treatment received. The study is registered at ClinicalTrials.gov, NCT03275285.
Findings Between Nov 15,2017, and March 21,2019,302 patients with a median of two previous lines of therapy were enrolled. 179 were randomly assigned to the isatuximab group and 123 to the control group. Median progression-free survival was not reached in the isatuximab group compared with 19.15 months (95% CI 15.77-not reached) in the control group, with a hazard ratio of 0.53 (99% CI 0.32-0-89; one-sided p=0-0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 136 (77%) of 177 patients in the isatuximab group versus 82 (67%) of 122 in the control group, serious TEAEs occurred in 105 (59%) versus 70 (57%) patients, and TEA Es led to discontinuation in 15 (8%) versus 17 (14%) patients. Fatal TEA Es during study treatment occurred in six (3%) versus four (3%) patients.
Interpretation The addition of isatuximab to carfilzomib-dexamethasone significantly improves progression-free survival and depth of response in patients with relapsed multiple myeloma, representing a new standard of care for this patient population. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
Filiaciones:
Moreau, P:
Univ Hosp Hotel Dieu, Dept Hematol, F-44093 Nantes, France
Dimopoulos, MA:
Natl & Kapodistrian Univ Athens, Athens, Greece
Mikhael, J:
City Hope Canc Ctr, Translat Genom Res Inst, Phoenix, AZ USA
Yong, K:
Univ Coll Hosp, Dept Haematol, London, England
Capra, M:
Hosp Mae de Deus, Ctr Integrado Hematol & Oncol, Porto Alegre, RS, Brazil
Facon, T:
Lille Univ Hosp, Lille, France
Hajek, R:
Univ Hosp Ostrava, Dept Hematooncol, Ostrava, Czech Republic
Univ Ostrava, Fac Med, Ostrava, Czech Republic
Spicka, I:
Charles Univ Prague, Dept Med 1, Dept Hematol, Fac Med 1, Prague, Czech Republic
Gen Hosp Prague, Prague, Czech Republic
Baker, R:
Murdoch Univ, Perth Blood Inst, Perth, WA, Australia
Kim, K:
Sungkyunkwan Univ, Sch Med, Dept Med, Div Hematol Oncol,Samsung Med Ctr, Seoul, South Korea
Martinez, G:
Univ Sao Paulo, Hosp Clin, Fac Med, Sao Paulo, Brazil
Min, CK:
Catholic Hematol Hosp, Dept Hematol, Seoul, South Korea
Leukemia Res Inst, Seoul, South Korea
Pour, L:
Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic
Leleu, X:
CHU, Serv Hematol & Therapie Cellulaire, Poitiers, France
INSERM, CIC 1402, Poitiers, France
:
Hosp Badalona Germans Trias & Pujol, Inst Josep Carreras, Badalona, Spain
Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Badalona, Spain
Univ Calif San Francisco, Dept Hematol, San Francisco, CA 94143 USA
Koh, Y:
Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea
Suzuki, K:
Japanese Red Cross Med Ctr, Myeloma Amyloidosis Ctr, Tokyo, Japan
Risse, ML:
Sanofi R&D, Vitry Sur Seine, France
Asset, G:
Sanofi R&D, Chilly Mazarin, France
Mace, S:
Sanofi R&D, Vitry Sur Seine, France
Martin, T:
Univ Calif San Francisco, Dept Hematol, San Francisco, CA 94143 USA
|