IMROZ is a large phase III study that was presented recently where patients who are elderly, transplant non-eligible were included to receive treatment by isatuximab VRd – bortezomib, lenalidomide, dexamethasone – so the quad regimen, versus VRd – bortezomib, lenalidomide, dexamethasone – as a control arm. Treatment was given continuously. So it was 440 patients included and the primary endpoint was progression free survival.

The data so far have been presented and we have seen a benefit in progression free survival for the patients receiving the quad regimen, Isa-VRd. So the 60 months rate of PFS was 63% – almost two-thirds of the patients are progression free at five years which is remarkable. The median PFS of the VRd arm, the control arm, was 54 months. So a clear benefit in progression free survival; the overall survival data are not mature yet.

Safety-wise it was well tolerated in those patients with no increased rate of infections or other treatment-emergent side effects per year.

Could you talk us through the methodology of the IMROZ frailty subgroup analysis?

So this subgroup analysis on frailty that we presented at this meeting is a post-hoc analysis so we used what we call the IFM simplified frailty score. It’s a frailty score based on ECOG performance status, age and the Charlson Comorbidities Index. So we are able to stratify the patients based on their frailty. We have two groups, the frail and the non-frail patients. So in IMROZ it was 130 patients who were frail and 310 patients who were not frail.

It's important to say that in IMROZ patients were younger than 80 years old, so patients above 80 years old were excluded. So we have patients who are frail per ECOG performance status or per Charlson Comorbidities but not per age.

What were the key results of this analysis?

The results are, I think, very interesting because we observe in the frail population of patients a benefit of the quad regimen, Isa-VRd, versus VRd. So the benefit is observed in frail and in the non-frail population with a hazard ratio of 0.78 and 0.79 respectively. The quality of life is preserved in both groups, frail and non-frail, receiving the quad regimens. There are no added side effects in the frail population of patients. The most frequent side effect is haematologic side effects and neutropenia and then it’s infections but there is no major increase of side effects in the frail population of patients.

So that’s a good indication that the quad is feasible even in the frail population of patients. Of course it’s a selected frail population of patients because they are below 80 years old but still we can do the quad for all those patients and it’s efficient and the safety profile is very much manageable.

What could be the impact of these results?

We are very excited to have this new combination available, hopefully soon, with the quad regimens. It’s also changing the way we treat these elderly patients, probably with two different subgroups of patients – the ones who will be eligible for the quad and the ones who will not be eligible for the quad. So we also have to work on this frailty score and how we evaluate those patients to stratify them in the best way possible. So it’s new options and with, again, improving the outcome of those patients which is remarkable.

Where does the study and this latest analysis sit in the treatment landscape?

I think these quad regimens will become the new standard of care treatment for the elderly fit population of patients, that’s clear. The question is where can we move this quad regimen in the landscape of the transplant eligible patients and, of course, how frail the patients can be and receive the quad regimen. So this study is bringing some interesting data. It’s the only study with the quad for transplant non-eligible that can assess this question because in the two others, CEPHEUS and BENEFIT, the frail population of patients were excluded by inclusion/exclusion criteria. So it’s only in IMROZ that we could do this analysis of frailty.

Now in the future we’ll probably have to develop some quad-light regimens, as we did for the VRd-light as well, to be able to treat more frail patients or more elderly patients with the quad in the future. That will be very interesting to improve the outcome.