Real-world evidence of the use of carfilzomib to refractory to lenalidomide patients

Prof Evangelos Terpos - University of Athens, Athens, Greece

This study had to do also with real-world evidence for the use of carfilzomib-based regimens, approved carfilzomib-based regimens, in patients who had been previously exposed or they are refractory to lenalidomide. This is very important, so it is part of the previous study, it is a sub-analysis of the study that I previously described to you, but it is very important because it includes patients who are refractory to lenalidomide, something that is of extreme interest as we do know that these patients probably have a poor prognosis compared to the other myeloma patients.

So in this specific sub-analysis we managed to have 151 patients who were refractory to lenalidomide and we compared their results with 122 patients on the same study who were non-refractory to lenalidomide.

Could you highlight the methodology and results of the study?

As I told you, this was the result of a study, a real-world study that, as I previously mentioned, we conducted in several European countries. In this specific sub-analysis we wanted to check the refractory to lenalidomide patients who were treated with either KRd or Kd and compared the efficacy and safety for those who were not refractory to lenalidomide.
So, for KRd patients 74 of them were refractory to lenalidomide and another 308 were not refractory to lenalidomide while with Kd we had a better balance, so 151 patients were refractory to lenalidomide and 122 who were not, suggesting that the Kd is preferred for the physicians treatment regimen for the lenalidomide refractory patients and I think that this is logical.

In both cohorts the overall response rate was higher among the non-lenalidomide refractory patients compared to the lenalidomide refractory but the overall response rate, for example, was better with KRd, it was 69%, versus 87% with the same combination for the non-lenalidomide refractory. While for Kd the overall response rate for lenalidomide refractory patients was 59% versus 80% for the non-lenalidomide refractory.

It is extremely important, the median time to discontinuation was much shorter for the lenalidomide refractory versus the non-lenalidomide refractory. So, for example, the median time to discontinuation for the KRd was 11.1 months for the lenalidomide refractory patients versus 16.2 months for the non-refractory to lenalidomide and the respective values for Kd were 6.3 months for lenalidomide refractory versus 9.7 for non-lenalidomide refractory. We have seen that carfilzomib was used according to the EU label so we haven’t had any problems with that and lenalidomide refractory patients in both cohorts experienced more serious adverse events and fatal events than the non-lenalidomide refractory patients. This is of extreme importance, for example for fatal adverse events we had around 7% in the lenalidomide refractory patients for KRd versus 2.6% for the non-lenalidomide refractory while for Kd it was 9% versus 7%. So this suggests also that the lenalidomide refractory population is a poor risk population.

To conclude for the results of the study, in this real-world cohort lenalidomide refractory patients had received more prior lines of therapy and were exposed to more agents than the non-lenalidomide refractory patients who had deep responses that were achieved for this difficult to treat population in this descriptive analysis which are consistent with the published subgroup analysis of the big clinical trials, ENDEAVOR and ASPIRE. I believe that this real-world data supports the use of carfilzomib for relapsed/refractory myeloma patients and emphasises the strength of Kd as a strong backbone therapy for lenalidomide refractory patients which, to my opinion, is a very difficult population to be treated.

What impact can these results have on the treatment of multiple myeloma?

Confirmation of the results of phase III studies of the sub-analysis of the phase III studies ENDEAVOR and ASPIRE regarding the lenalidomide refractory patients gives more strength to these results and suggests that carfilzomib and dexamethasone as backbone remains a very strong doublet for the treatment of lenalidomide refractory patients, possibly with the addition of other drugs like lenalidomide or daratumumab.