Carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma
Prof Ola Landgren - Memorial Sloan Kettering Cancer Center, New York City, USA
We have participated in a pooled analysis with several other groups that have treated patients that are newly diagnosed with multiple myeloma treated with the combination of carfilzomib, lenalidomide and dexamethasone, also referred to as KRD. In this pooled analysis merging four studies together has given us larger numbers. We have also been able to compare the outcome of patients who underwent bone marrow transplantation versus patients who did not undergo bone marrow transplantation after this combination therapy.
The high point of this presentation is that the KRD regimen delivers very high responses. The overall response rate is close to 100% for patients independent of transplantation or not. Specifically, if you look at the complete response rates patients who were treated with carfilzomib, lenalidomide and dexamethasone alone the complete response rate in this pooled analysis is more than 70%. If you add the transplantation it’s around 80%.
Looking at long-term clinical outcomes the study shows that the progression free survival is about the same. Certainly there are restrictions for the purpose of progression free survival interpretations with regards to how long patients were followed on each of these four different datasets. But with the current follow-up time the progression free survival looks very similar. That’s also true if you look at a time-point when the data is mature for overall survival.
When it comes to safety the KRD regimen is found to be very safe, very consistent with what we have seen previously. So in the current absence of a randomised phase III trial using KRD I think it’s quite reassuring to see that the pooling of four large efforts continues to build strong evidence that this is a very effective and safe regimen for newly diagnosed patients.
The KRD regimen is already listed as a standard of care treatment for patients with multiple myeloma in the United States. The National Comprehensive Cancer Center Network, or NCCN, guideline stipulates which therapies are recommended and therefore also reimbursed. The two main regimens that are listed in this guideline are the VRD and the KRD regimens. Until very recently both these two regimens were based on phase II studies. In 2017 the first randomised study comparing VRD to RD was published. So therefore the category 2a, which is what you get if you have a phase II study, was increased to a category 1 for the VRD regimen. The VRD regimen was initially put in this guideline back in 2009 so it took many years for it to be upgraded from 2a to 1 but both category 1 and 2a are recommended and reimbursed.
