Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
Mené dans 16 pays sur 302 patients atteints d'un myélome multiple récidivant, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de l'isatuximab à un traitement combinant carfilzomib et dexaméthasone
Background : Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide–dexamethasoneand 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, andthe Asia-Pacific region. Patients with relapsed or refractory multiple myeloma agedat least 18 years who had received one to three previous lines of therapy and hadmeasurable 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 intravenouslyweekly for the first 4 weeks, then every 2 weeks. Both groups received the approvedschedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatmentcontinued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assignedtreatment. Safety was assessed in all patients who received at least one dose accordingto 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 groupand 123 to the control group. Median progression-free survival was not reached inthe isatuximab group compared with 19·15 months (95% CI 15·77–not reached) in thecontrol 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 discontinuationin 15 (8%) versus 17 (14%) patients. Fatal TEAEs during study treatment occurred insix (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, representinga new standard of care for this patient population.
The Lancet 2021