IMS 2026 | Long-term outcomes with KRd versus Rd in high-risk smoldering multiple myeloma

EMN15/HOV-147 was designed because at that time there was no trial in high-risk mono and multiple myeloma that compared an intensive treatment regimen with a less intensive treatment regimen. And we therefore investigated whether the addition of carfilzomib to lenalidomide and dexamethasone would improve response depth and is able to delay progression to multiple myeloma in high-risk smoldering multiple myeloma patients and patients were therefore enrolled to receive either nine cycles of KRd induction versus nine cycles of Rd induction and with a median follow-up of 45 months as the trial is there now we looked at first at the primary endpoint which was MRD negativity after nine cycles of induction treatment and this was in favor of KRd compared to nine cycles of induction with Rd and this also applies for the response categories so the responses were much better in KRd when we compare this to Rd and if we then have a look at the progression-free survival in particular, particularly which is the biochemical and the clinical progression-free survival we saw that this was also in favor of KRd when we compare this to Rd with a 3-year PFS of approximately 82% in KRd patients versus approximately 45% of patients in Rd. So that’s quite a huge difference between them two. What we know is that KRd is able to delay progression to myeloma biochemically and clinically, as has been shown in the 3-year PFS of 82 versus 42. We do see that the curves are getting on and on. We are not at a plateau phase yet, but we’ll know what the future will tell us. Regarding deaths, we saw no deaths in the KRd group and we did see two deaths in the Rd group: one patient died of a cerebral bleeding and one patient died of progression to multiple myeloma with a secondary plasma cell leukemia, but both were considered as not treatment-related. When we look at the occurrence of any adverse events, we saw that every patient treated with KRd experienced an adverse event versus almost every patient in Rd. And when we have a look, in particular, in grade three or higher adverse events, we saw that this was more common in KRd versus Rd; however, this was: there were a lot of grade 3 adverse events, but not that many grade 4 adverse events, and grade 5 adverse events did not occur at all in both groups. And when we have a look at the origin of those adverse events, we see that infections are the most common. Cardiac events weren’t that common or not as common as we expected, since carfilzomib could be cardiotoxic. And of the infections, pneumonia was the most common. So we can say that there is more toxicity also at the long-term follow-up. So for the induction and extended treatment period, when we look at carfilzomib, lenalidomide, and dexamethasone. However, this was manageable toxicity. We had no new safety concerns. So, we can say it is manageable toxicity and we had no new insights, but there was more toxicity for the patients that have been treated with carfilzomib when we compare this to lenalidomide and dexamethasone.

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