1. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
- Author
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Philippe Moreau, Meletios-Athanasios Dimopoulos, Joseph Mikhael, Kwee Yong, Marcelo Capra, Thierry Facon, Roman Hajek, Ivan Špička, Ross Baker, Kihyun Kim, Gracia Martinez, Chang-Ki Min, Ludek Pour, Xavier Leleu, Albert Oriol, Youngil Koh, Kenshi Suzuki, Marie-Laure Risse, Gaelle Asset, Sandrine Macé, Thomas Martin, Ivan Spicka, Kim Kihyun, Min Chang-Ki, Koh Youngil, Tom Martin, Hang Quach, Andrew Lim, Helen Crowther, Hanlon Sia, Cyrille Hulin, Mohamad Mohty, Gabor Mikala, Zsolt Nagy, Marta Reinoso Segura, Laura Rosinol, Munci Yagci, Mehmet Turgut, Mamta Garg, Gurdeep Parmar, Brad Augustson, Nelson Castro, Edvan Crusoe, Tomas Pika, Sosana Delimpasi, Kenichi Ishizawa, Anup George, Tatiana Konstantinova, Javier De La Rubia, Kim Sung-Hyun, Angelo Maiolino, Anthony Reiman, Richard LeBlanc, Shigeki Ito, Junji Tanaka, Alexander Luchinin, Irina Kryuchkova, Joaquin Martinez, Jesse Shustik, Lionel Karlin, Anargyros Symeonidis, Miklos Egyed, Mario Petrini, Michele Cavo, Michihiro Uchiyama, Hilary Blacklock, Mutlu Arat, James Griffin, Hannah Hunter, Tonda Buck, Achilles Anagnostopoulos, Konstantinos Konstantopoulos, Tamas Masszi, Sara Bringhen, Barbara Gamberi, Yawara Kawano, Kim Jin Seok, Hakan Ozdogu, Fahir Ozkalemkas, Moreau P., Dimopoulos M.-A., Mikhael J., Yong K., Capra M., Facon T., Hajek R., Spicka 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., Mace S., Martin T., Kihyun K., Chang-Ki M., Youngil K., 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.
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Male ,medicine.medical_specialty ,Population ,Anti-Inflammatory Agents ,Phases of clinical research ,Administration, Intravenou ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,Dexamethasone ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immunologic Factor ,Recurrence ,Internal medicine ,Clinical endpoint ,Medicine ,Humans ,Immunologic Factors ,030212 general & internal medicine ,Prospective Studies ,education ,Multiple myeloma ,Aged ,Isatuximab ,education.field_of_study ,business.industry ,Hazard ratio ,General Medicine ,Middle Aged ,medicine.disease ,Carfilzomib ,Progression-Free Survival ,Discontinuation ,Thalidomide ,Anti-Inflammatory Agent ,Prospective Studie ,chemistry ,Oligopeptide ,Administration, Intravenous ,Drug Therapy, Combination ,Female ,business ,Multiple Myeloma ,Oligopeptides ,Human - 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 abstractYouTube link: https://youtu.be/5kXtQQlzRh4
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- 2020