1. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
- Author
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Moreau, P., Dimopoulos, M-A, Mikhael, J., Yong, K., Capra, M., Facon, T., Hajek, R., Špička, I., Baker, R., Kim, K., Martinez, G., Min, C-K, Pour, L., Leleu, X., Oriol, A., Koh, Y., Suzuki, K., Risse, M-L, Asset, G., Macé, S., Martin, T., Quach, H., Lim, A., Crowther, H., Sia, H., Hulin, C., Mohty, M., Mikala, G., Nagy, Z., Reinoso Segura, M., Rosinol, L., Yagci, M., Turgut, M., Garg, M., Parmar, G., Augustson, B., Castro, N., Crusoe, E., Pika, T., Delimpasi, S., Ishizawa, K., George, A., Konstantinova, T., De La Rubia, J., Sung-Hyun, K., Maiolino, A., Reiman, A., LeBlanc, R., Ito, S., Tanaka, J., Luchinin, A., Kryuchkova, I., Martinez, J., Shustik, J., Karlin, L., Symeonidis, A., Egyed, M., Petrini, M., Cavo, M., Uchiyama, M., Blacklock, H., Arat, M., Griffin, J., Hunter, H., Buck, T., Anagnostopoulos, A., Konstantopoulos, K., Masszi, T., Bringhen, S., Gamberi, B., Kawano, Y., Jin Seok, K., Ozdogu, H., Ozkalemkas, F., Moreau, P., Dimopoulos, M-A, Mikhael, J., Yong, K., Capra, M., Facon, T., Hajek, R., Špička, I., Baker, R., Kim, K., Martinez, G., Min, C-K, Pour, L., Leleu, X., Oriol, A., Koh, Y., Suzuki, K., Risse, M-L, Asset, G., Macé, S., Martin, T., Quach, H., Lim, A., Crowther, H., Sia, H., Hulin, C., Mohty, M., Mikala, G., Nagy, Z., Reinoso Segura, M., Rosinol, L., Yagci, M., Turgut, M., Garg, M., Parmar, G., Augustson, B., Castro, N., Crusoe, E., Pika, T., Delimpasi, S., Ishizawa, K., George, A., Konstantinova, T., De La Rubia, J., Sung-Hyun, K., Maiolino, A., Reiman, A., LeBlanc, R., Ito, S., Tanaka, J., Luchinin, A., Kryuchkova, I., Martinez, J., Shustik, J., Karlin, L., Symeonidis, A., Egyed, M., Petrini, M., Cavo, M., Uchiyama, M., Blacklock, H., Arat, M., Griffin, J., Hunter, H., Buck, T., Anagnostopoulos, A., Konstantopoulos, K., Masszi, T., Bringhen, S., Gamberi, B., Kawano, Y., Jin Seok, K., Ozdogu, H., and Ozkalemkas, F.
- Abstract
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
- Published
- 2021