Daratumumab plus bortezomib/lenalidomide/dexamethasone in transplant-eligible patients with NDMM: MRD analysis

Dr Paula Rodríguez-Otero - Clinica Universidad de Navarra, Pamplona, Spain

I will be presenting the minimal residual disease analysis from the phase III randomised PERSEUS trial. Briefly, just to put it in context, PERSEUS is a randomised phase III study that is comparing daratumumab in combination with VRd induction, transplant and consolidation followed by DR maintenance, daratumumab/lenalidomide maintenance, versus the standard VRd induction followed by transplant followed by consolidation and lenalidomide maintenance.

The primary results of this trial were presented at ASH last year. In summary, D-VRd resulted in a significant improvement in progression free survival over VRd and also an increase in the depth of response, a higher proportion of complete response, a higher proportion of minimal residual disease negativity. We are presenting more results about the maintenance phase and a minimal residual disease analysis.

So the key takeaways of the presentation are that D-VRd induction consolidation followed by DR maintenance significantly increased the proportion of patients achieving minimal residual disease negativity, both at 10-5 and 10-6. So there is a deepening of the responses across the treatment and more profound during the maintenance part. This deepening of the responses occurs more frequently in the daratumumab arm as compared to the standard arm.

So when we go for the subgroup analysis for MRD 10-5 or 10-6 we do see a significant benefit for daratumumab plus VRd followed by DR maintenance across all prespecified subgroups, including patients with older age, patients with ISS 3 or high risk disease, both 10-5 and also in 10-6  threshold. If we speak about sustained MRD negativity, at least one year or more, or 18 months or more, we do see again a higher proportion of patients in the D-VRd plus DR arm achieving sustained MRD negativity, both 10-5 and 10-6 as compared to the VRd regime. Again, in the subgroup analysis there is a benefit across all prespecified subgroups including, again, older age, high risk disease, ISS stage 3.

So if we analyse patients that were defined as having high risk cytogenetic abnormalities, in this study the definition was either patients with deletion 17p, 4-14 or 14-16, we do see the same. So patients that were allocated to the experimental arm, D-VRd plus DR, they had a higher rate of MRD negativity, both 10-5 and, most importantly for high risk patients also in the deepest level, so 10-6 and also a higher proportion that were able to sustain MRD negativity in the D-VRd arm versus the VRd arm. This translated into a benefit in progression free survival.

Another aspect that I found is very relevant for this study and it speaks about the importance of continuing on therapy is that the proportion of patients that were able to convert from MRD positivity at the end of consolidation to MRD negativity or sustained MRD negativity during maintenance was higher in the D-VRd arm as compared to the VRd arm. So all this data overall reinforces this treatment, D-VRd induction, consolidation followed by DR maintenance, as the new standard for transplant eligible newly diagnosed myeloma patients.

So the impact is that we have a new standard of care and the biggest impact, I would say, is that we will have probably a new maintenance therapy to be proposed to our patients, really aiming for these very deep responses.