I presented data from the UK MRA Myeloma XI study. This was a very large study performed all around the UK and within the study we were able to compare a quadruplet combination as induction therapy for newly diagnosed myeloma patients compared to a triplet approach. So the quadruplet included the combination of carfilzomib, cyclophosphamide, lenalidomide and dexamethasone and we were able to compare outcomes for this quadruplet within the study to those for patients who had received the triplet of cyclophosphamide, lenalidomide and dexamethasone. So essentially with or without the carfilzomib included.
What was the study design?
This was a phase III trial for newly diagnosed myeloma patients who were considered fit to undergo autologous stem cell transplant. The study initially compared two different triplets, one comparing thalidomide and one lenalidomide, and then the study was adapted when the second generation proteasome inhibitor carfilzomib became available, to look at the combination of carfilzomib alongside the lenalidomide triplet. Patients were randomised, therefore, between those two approaches, between the quadruplet or one of the triplets as induction therapy.
What are the key results?
The results for progression free survival for this comparison have been previously presented and showed a significant improvement in progression free survival with the addition of carfilzomib to the triplet compared to those who didn’t receive the carfilzomib alongside the cyclophosphamide, lenalidomide and dexamethasone.
What we presented at ASH this year was the overall survival data for the study for this comparison after we have done almost ten years of follow-up of the patients within the trial. What we found was a significant improvement for overall survival for those patients who received the quadruplet combination compared to the triplet.
What is the clinical significance of these results?
Our study really showed the importance of combining a proteasome inhibitor and immunomodulatory drug up front. We have seen that that approach was better than using a response adapted approach, so using only a proteasome inhibitor for those patients who had a less deep response to their initial IMiD induction triplet.
What’s important is that as we go forward we have now seen results from other studies that have shown the addition of an anti-CD38 antibody even into that mix, on top of the proteasome inhibitor and IMiD combination, seems to also show additional benefit and is now standard of care worldwide.
But, really importantly, what we showed is that really long-term follow-up of large academic trials enables us to read out overall survival data and it really is necessary to follow up these studies for a long time to get that kind of granularity of data and be able to show these incremental improvements in overall survival that we have seen as treatments for myeloma have evolved over time.
