The IKEMA study is a phase III randomised study in patients with relapsed myeloma comparing carfilzomib and dexamethasone, one of the standards of care, versus carfilzomib dexamethasone plus isatuximab. Isatuximab is a monoclonal antibody targeting CD38. Patients were enrolled when they had at least one prior line of treatment, one to three prior lines of treatment, and they received either carfilzomib and dexamethasone, Kd, at the dose of 56mg for carfilzomib, or the same combination plus isatuximab IV, 10mg/kg, weekly during the first cycle and subsequently every two weeks. The primary endpoint of the study was progression free survival and we have reported at EHA the pre-specified interim analysis for progression free survival.
The patient characteristics were well balanced in the two arms of the study. We had 10% of the patients above the age of 75, one fourth of the patients with high risk cytogenetics. The median number of prior lines of treatment was two and also 30% of the patients were refractory to lenalidomide at the time of study entry.
So the primary endpoint, PFS, the median PFS in the control arm, the Kd arm, was 19.1 months, so that’s a good control arm. When thinking about the pivotal study for the approval of Kd, the ENDEAVOR study, the median PFS was 18.7 months. So definitely a good Kd arm and if you are adding isatuximab we are improving progression free survival with a hazard ratio of 0.53. This is representing a 47% reduction in the risk of progression or death so definitely a very good hazard ratio in favour of the triplet combination. This PFS benefit was observed across all subgroups of patients and also as a secondary endpoint we looked at the depth of response. Overall response rate was very high in the two arms of the study but much higher in the isatuximab arm. We looked as well at minimal residual disease negativity and the rate of MRD negativity was 30% by NGS 10-5 in the isatuximab arm versus 13% only with Kd alone.
Other secondary endpoints: time to next treatment was delayed, significantly delayed, with a hazard ratio of 0.56 in the isatuximab arm and also we looked at overall survival but those data are not mature because of the short follow-up. The study is ongoing and we will present overall survival data later.
What about now toxicity? With the addition of isatuximab we are not adding any significant toxicity. The discontinuation rate is identical in the two arms of the study. The fatal adverse event rates are also similar in both arms. The infusion related reactions with isatuximab were reported only during cycle 1 and only grade 1 or 2 so definitely the triplet combination is feasible and manageable.
So, to conclude, we can say that IKEMA met its primary endpoint with a significant benefit for progression free survival and this hazard ratio, this very good hazard ratio, of 0.53 with a benefit across multiple subgroups of patients. The safety profile is rather good, in fact, with a favourable risk benefit for patients with relapsed myeloma.
So this study potentially will be the pivotal study for the approval of Kd-isatuximab for relapsed myeloma.