Real-world evidence of the use of carfilzomib among multiple myeloma patients across 10 European countries and Israel
Prof Evangelos Terpos - University of Athens, Athens, Greece
Our first study had to do with real-world evidence of the use of carfilzomib among multiple myeloma patients with at least one prior therapy across ten European countries and Israel. We managed to have approximately 700 patients, in total it was 701 to be honest, and these patients received either KRd or Kd, the vast majority, because we excluded some patients who received other triplets, some combinations with cyclophosphamide or pomalidomide. So in total we had 382 patients who received KRd and 273 patients who received Kd. So the study in general evaluated the real-world effect of KRd and Kd in relapsed/refractory patients.
Could you highlight the methodology and results of the study?
This study is a standard real-world design that after a period that the patients had to receive at least one dose of carfilzomib, who had a period of recording the data, it was a study that was supported by Amgen. The main characteristic, the main result is that the KRd patients had received a median of one prior line of therapy while the Kd patients were more heavily pre-treated with a median of three prior lines. This is important because it shows that due to the use of lenalidomide previously carfilzomib and dexamethasone is probably given mainly in the more advanced disease.
A high overall response rate was seen in KRd patients with overall response rates of around 84% and it was 68% for the Kd patients but, as I told you, these were more heavily pre-treated with three prior lines of treatment. The deeper responses were seen in earlier lines of therapies for both KRd and Kd and that is why in KRd we had such a big overall response rate.
Regarding the dose that was given, on average carfilzomib was administered per the EU label in the KRd cohort and with dose adjustments in the Kd cohort. The median RDI, as we call it, the median reduction that happened in the Kd cohort was approximately 83%. If we see what is happening in the real world regarding treatment duration, the treatment duration with KRd was 14.6 months and for Kd 7.5 months, suggesting that what we expected from the clinical trials, more or less, we see in the real world.
The safety also was totally similar and the conclusion of this study is that in this real-life setting the KRd use was in accordance with the EU label, inducing high responses and maintaining treatment for a long duration. Compared with KRd patients, on the other hand, Kd was used in later lines to treat older and more heavily pre-treated patients with refractory disease. We have seen, more or less, very good duration of treatment, especially with KRd, which is similar to what has been described in the phase III trials which gave licence to the combinations. The benefit-risk profile of KRd and Kd in the real world was also consistent with the clinical trial results from the two studies that I previously mentioned which were ASPIRE and ENDEAVOR respectively.
What impact can these results have on the treatment of multiple myeloma?
The important result of this study was that the duration of treatment and safety and efficacy of both combinations are similar to the ENDEAVOR and ASPIRE studies, suggesting that the physicians who are dealing with myeloma therapy could expect similar efficacy and safety with what they see in the clinical trials.
We do know that many times patients who do not participate in clinical trials, the patients that we see every day, have comorbidities. They are patients who cannot participate in clinical trials in a big proportion and so we are wondering if the results that we are reading, or the results that we have seen participating in these phase III clinical studies, is the same in the real-world life. I believe that this makes the physicians feel much better giving these combinations in the everyday patients with multiple myeloma and I believe that they could expect similar effects and safety profile and adverse events with what they have read in the phase III studies.