ASH 2024 | The Myeloma XI trial: adding carfilzomib to cyclophosphamide, lenalidomide, and dexamethasone

So I presented the final analysis of the Myeloma XI trial here at ASH this year. This is an academic trial led by a number of clinicians from around the UK and that recruited more than 4,000 patients from 110 NHS hospitals. It was a trial that was initially designed to compare the oral IMiD triplet, cyclophosphamide, thalidomide, and dexamethasone to cyclophosphamide, lenalidomide, and dexamethasone using a response-adapted approach with intensification to a proteasome inhibitor, bortezomib, for patients who had a less deep response. During the course of the study, the second-generation proteasome inhibitor carfilzomib became available and we rapidly adapted the study to try and incorporate the use of carfilzomib in an upfront quadruplet during the course of the trial. So this means that we can compare patients who receive the quadruplet with carfilzomib, cyclophosphamide, lenalidomide, and dexamethasone to those who had the triplet cyclophosphamide, lenalidomide, and dexamethasone upfront. We’ve been following these patients up now for a median of almost 10 years, and so we have good long-term follow-up data. And what I presented here was the outcome for progression-free and overall survival in these patients. And what we saw was that the addition of carfilzomib to the triplet, making this quadruplet combination, was associated with significantly prolonged progression-free and overall survival. I think what was really exciting for us was that we can see the overall survival of patients in trials across the UK really increasing over time in a really dramatic and excellent way over the last 30 years or so, since some of the earlier UK trials in the 1990s all the way through to the Myeloma XI trial that we presented here.

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