Myeloma 11 Trial: Carfilzomib Quadruplet Enhances Overall Survival | Charlotte Pawlyn, MD | #ASH24

My name is Charlotte Paulin. I work at the Royal Marsden Hospital and the Institute of Cancer Research in London and I'm part of the UK Myeloma Research Alliance, a group of academic myeloma clinicians in the UK who design and run clinical trials. I'm here at ASH in San Diego presenting data from the Myeloma 11 trial. This was a trial that we presenting long-term follow-up data from the study that now has more than 10 years worth of follow-up, so a median of 10 years worth of follow-up. The study was designed really to look at two different approaches. It was initially looking at the combination of the oral drug lenalidomide compared to thalidomide, both of which were given in combination with cyclophosphamide and dexamethasone and that was given in a response adapted approach. So if patients hadn't had a very deep response to their first treatment, they then could have a treatment after that before going on to stem cell transplant. During the study, the second generation proteasome inhibitor, so a new proteasome inhibitor called carfilzomib was being developed and we adapted the study to introduce this drug in combination with the cyclophosphamide, lenalidomide and dexamethasone as quickly as possible to try and study whether this was a better approach than the response adapted approach and see if we could give patients the opportunity to have that combination as quickly as possible. So I was presenting data comparing this quadriplet of drugs, so four drugs combined together, compared to the triplet response adapted approach. What we found was that adding the carfilzomib into the triplet both significantly increased the time until patients' disease progressed, but in the data I've presented here also improved overall survival over the course of the study. And we can only really see that by following patients up for a really long time and collecting data for a long, long time because as we know in outcomes for myeloma patients have improved a lot over time and therefore it takes a long time to see these differences. But we were delighted to report that the addition of carfilzomib does improve overall survival compared to the triplet approach. This study was obviously done in the era before anti-CD38 antibodies like daratumumab or isotuxumab had become available and they are now often used in combinations up front as well. But nevertheless we saw very good long-term outcomes even without those drugs in combination in this study.