ASCO 2025 | Long-term outcomes from the ENDURANCE trial: VRd versus KRD in newly diagnosed myeloma

So the ENDURANCE trial originally presented and published back in 2020 was a Phase III trial that enrolled a little over a thousand patients, randomizing newly diagnosed myeloma patients to receiving either a bortezomib-based triplet VRd or a carfilzomib-based triplet KRd. We had originally published that there is no difference in the progression-free survival or the overall survival between VRd and KRd when used as induction therapy in primarily a standard risk population, though they did include patients with t(4;14) translocation and 1q abnormalities. 

Now, this represents a longer-term follow-up with a median follow-up of nearly five years. Now, we can, again, demonstrate that the lack of difference in the progression-free survival between the two different triplets is maintained, and we still don’t see any difference in the overall survival. But with the longer-term follow-up, we were able to do some additional sensitivity analysis, particularly looking at patients who went off therapy early on. And if you were to look at patients who got censored for alternate therapy and consider those as maybe events, then we see that maybe there is a trend towards improved PFS in the KRd population in certain subgroups. But we have also previously published that there is probably a better PFS for KRd in patients with high-risk disease if you look at 1q abnormality. 

So I think the bottom line with a longer term follow-up is that in general, KRd does not offer an advantage over VRd in the general patient population. And given that we are not using triplets anymore, this newly diagnosed, this data again supports the selection of VRd as the combination to which CD38 monoclonal antibodies or other new agents should be added versus using KRd. Having said that, there might be a role for K-based combinations, especially in the younger patient population who are more fit and less likely to get some of the toxicities associated with carfilzomib and also patients with high-risk disease. 

So we certainly have data from, you know, several of those K combinations like the IsaKRd from the IsKia trial, from the MIDAS trial, and from the ADVANCE trial, all of which are presented at ASCO. So again, showing that it’s a good regimen, highly effective, high MRD negativity rate, but we just lack the data that everybody should be getting KRd-based combinations.

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