Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Issue 10292 (19th June 2021)

• Record Type: Journal Article
• Authors: Moreau, Philippe; Dimopoulos, Meletios-Athanasios; Mikhael, Joseph; Yong, Kwee; Capra, Marcelo; Facon, Thierry; Hajek, Roman; Špička, Ivan; Baker, Ross; Kim, Kihyun; Martinez, Gracia; Min, Chang-Ki; Pour, Ludek; Leleu, Xavier; Oriol, Albert; Koh, Youngil; Suzuki, Kenshi; Risse, Marie-Laure; Asset, Gaelle; Macé, Sandrine; Martin, Thomas; Moreau, Philippe; Dimopoulos, Meletios-Athanasios; Mikhael, Joseph; Yong, Kwee; Capra, Marcelo; Facon, Thierry; Hajek, Roman; Spicka, Ivan; Baker, Ross; Kihyun, Kim; Martinez, Gracia; Chang-Ki, Min; Pour, Ludek; Leleu, Xavier; Oriol, Albert; Youngil, Koh; Suzuki, Kenshi; Martin, Tom; Quach, Hang; Lim, Andrew; Crowther, Helen; Sia, Hanlon; Hulin, Cyrille; Mohty, Mohamad; Mikala, Gabor; Nagy, Zsolt; Reinoso Segura, Marta; Rosinol, Laura; Yagci, Munci; Turgut, Mehmet; Garg, Mamta; Parmar, Gurdeep; Augustson, Brad; Castro, Nelson; Crusoe, Edvan; Pika, Tomas; Delimpasi, Sosana; Ishizawa, Kenichi; George, Anup; Konstantinova, Tatiana; De La Rubia, Javier; Sung-Hyun, Kim; Maiolino, Angelo; Reiman, Anthony; LeBlanc, Richard; Ito, Shigeki; Tanaka, Junji; Luchinin, Alexander; Kryuchkova, Irina; Martinez, Joaquin; Shustik, Jesse; Karlin, Lionel; Symeonidis, Anargyros; Egyed, Miklos; Petrini, Mario; Cavo, Michele; Uchiyama, Michihiro; Blacklock, Hilary; Arat, Mutlu; Griffin, James; Hunter, Hannah; Buck, Tonda; Anagnostopoulos, Achilles; Konstantopoulos, Konstantinos; Masszi, Tamas; Bringhen, Sara; Gamberi, Barbara; Kawano, Yawara; Jin Seok, Kim; Ozdogu, Hakan; Ozkalemkas, Fahir;
• Is Part Of: Lancet. Volume 397:Issue 10292(2021)
• Page Start: 2361
• Page End: 2371
• Publication Date: 2021-06-19
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Medicine; Electronic journals; Periodicals; 610.5
• DOI: 10.1016/S0140-6736(21)00592-4
• Languages: English
• ISSNs: 0140-6736

Abstract

Summary: 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, open-label study compared the efficacy of isatuximab plus carfilzomib–dexamethasone versus carfilzomib–dexamethasone in patients with relapsed multiple myeloma. 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 myeloma 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 the 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 TEAEs led to discontinuation in 15 (8%) versus 17 (14%) patients. Fatal TEAEs 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. Funding: Sanofi. Video Abstract: Video abstract YouTube link: https://youtu.be/5kXtQQlzRh4