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Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.

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Title: Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.
Authors: Moreau, Philippe (AUTHOR), Dimopoulos, Meletios-Athanasios (AUTHOR), Mikhael, Joseph (AUTHOR), Yong, Kwee (AUTHOR), Capra, Marcelo (AUTHOR), Facon, Thierry (AUTHOR), Hajek, Roman (AUTHOR), Špička, Ivan (AUTHOR), Baker, Ross (AUTHOR), Kim, Kihyun (AUTHOR), Martinez, Gracia (AUTHOR), Min, Chang-Ki (AUTHOR), Pour, Ludek (AUTHOR), Leleu, Xavier (AUTHOR), Oriol, Albert (AUTHOR), Koh, Youngil (AUTHOR), Suzuki, Kenshi (AUTHOR), Risse, Marie-Laure (AUTHOR), Asset, Gaelle (AUTHOR), Macé, Sandrine (AUTHOR)
Source: Lancet. 6/19/2021, Vol. 397 Issue 10292, p2361-2371. 11p.
Subjects: Multiple myeloma, Survival rate, Sanofi SA, Progression-free survival, Dexamethasone, Monoclonal antibodies
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 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. [ABSTRACT FROM AUTHOR]
Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.
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  Data: <searchLink fieldCode="AR" term="%22Moreau%2C+Philippe%22">Moreau, Philippe</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dimopoulos%2C+Meletios-Athanasios%22">Dimopoulos, Meletios-Athanasios</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mikhael%2C+Joseph%22">Mikhael, Joseph</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yong%2C+Kwee%22">Yong, Kwee</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Capra%2C+Marcelo%22">Capra, Marcelo</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Facon%2C+Thierry%22">Facon, Thierry</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hajek%2C+Roman%22">Hajek, Roman</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Špička%2C+Ivan%22">Špička, Ivan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Baker%2C+Ross%22">Baker, Ross</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kim%2C+Kihyun%22">Kim, Kihyun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Martinez%2C+Gracia%22">Martinez, Gracia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Min%2C+Chang-Ki%22">Min, Chang-Ki</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pour%2C+Ludek%22">Pour, Ludek</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Leleu%2C+Xavier%22">Leleu, Xavier</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Oriol%2C+Albert%22">Oriol, Albert</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Koh%2C+Youngil%22">Koh, Youngil</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Suzuki%2C+Kenshi%22">Suzuki, Kenshi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Risse%2C+Marie-Laure%22">Risse, Marie-Laure</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Asset%2C+Gaelle%22">Asset, Gaelle</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Macé%2C+Sandrine%22">Macé, Sandrine</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. 6/19/2021, Vol. 397 Issue 10292, p2361-2371. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Multiple+myeloma%22">Multiple myeloma</searchLink><br /><searchLink fieldCode="DE" term="%22Survival+rate%22">Survival rate</searchLink><br /><searchLink fieldCode="DE" term="%22Sanofi+SA%22">Sanofi SA</searchLink><br /><searchLink fieldCode="DE" term="%22Progression-free+survival%22">Progression-free survival</searchLink><br /><searchLink fieldCode="DE" term="%22Dexamethasone%22">Dexamethasone</searchLink><br /><searchLink fieldCode="DE" term="%22Monoclonal+antibodies%22">Monoclonal antibodies</searchLink>
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  Data: <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Findings: </bold>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.<bold>Interpretation: </bold>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.<bold>Funding: </bold>Sanofi. VIDEO ABSTRACT. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1016/S0140-6736(21)00592-4
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