KRd consolidation in MM patients with a positive PET-CT after standard first-line therapy: Results from the phase II CONPET trial

Dr Fredrik Schjesvold - Oslo University Hospital, Oslo, Norway

We presented the CONPET study yesterday. It’s a study in transplant eligible first line patients who have received standard induction therapy, it could be VRd, VTd or VCd but it’s mostly VRd. They performed that and then a transplant and after that they were screened for the study. You could screen them within twelve months after they started therapy. Within the screening period we did a PET-CT with FDG-PET, if that was positive, which is a bad prognostic sign for these patients with myeloma, they were enrolled into the study. So the study was about giving them an intensified consolidation treatment to see if we could get the patients to go from PET-CT positivity to PET negativity and do something with this bad prognostic signal.

This is early data still. We have screened 64 patients and enrolled 25, so 38% were PET positive of this population. We only screened patients who were in at least VGPR, so were already in a good response, and of those 38% were PET positive which is not good. Those patients are receiving KRd consolidation, that is carfilzomib, Revlimid and dexamethasone, and so far 14 patients have gone through this treatment and been evaluated with a new PET afterwards. Of these 14 patients nine patients had an improvement in PET after this consolidation treatment. Only three went from positive to negative because that’s a binary feature but if you looked at the volume of positivity, nine altogether went down and improved on the PET. It also shows a problem with PET that it’s either positive or negative when it’s actually just a long scale. So we need to be able to make a better global evaluation of this from PET pictures, PET images. We’re going to use the pictures from this, images from this study, to try to evaluate how to do that also.
We also did MRD samples from bone marrow before and after the treatment. As shown in several other studies it’s really complementary because patients with PET positivity can be both MRD negative and MRD positive in bone marrow and the opposite. So these are two very different ways of measuring residual disease and we depend on both for today.

Are there any potential clinical implications at this point?

It’s a bit too early to say. So what we see is that nine out of 14 patients, a small sample size so far, but are improving on their PET. So whether that will give a clinical benefit or not is difficult to tell from such a small trial but we are also following the PET negative patients that at screening have a better prognosis than the patients we are treating. So we could be able to spot a signal if the difference between these groups is not as it would have been without the consolidation treatment. But that’s for longer follow-up.

Is there anything you would like to add?

I have one thing, because when you have patients who after treatment still have residual disease, especially on PET, that’s a bad sign. Consolidation, I think you need to do something really extra to have a large impact. So I think it would be interesting if they have spots of residual disease to, at the same time as you did consolidation or intensification of some kind, also irradiate those spots. In those spots there are probably present the cells that will make the most problematic relapse at some point in the future and with radiation we might be able to take out them at least.