The CASSIOPEIA trial we have now a median follow-up of nearly seven years, so it’s an old trial now. It randomised newly diagnosed myeloma patients transplant eligible between two groups, two arms, VTd or dara-VTd induction consolidation and a graft in the two arms. For patients who were able to achieve a partial response to this first step there was a second randomisation between two arms of maintenance – either daratumumab or just observation until two years, up to two years. This trial, everybody knows that this trial showed that the incorporation of an anti-CD38 with a triplet allowed to increase very significantly both PFS and OS in patients. But the presentation I gave here was about MRD because it was one of the first trials where we assessed MRD at many timepoints – post-induction, post-consolidation, during the maintenance phases at six months, one year, two years and after the maintenance during the follow-up phases, one year, two year, three years. This is important because we now know that one negative MRD timepoint is good but it’s better to have a maintained, a sustained, MRD negativity. So this follow-up is very important.
In this study we learned many things but in summary we learned that Flow and NGS techniques are equivalent, there is a very good correlation between the two techniques, because we assessed both at many timepoints in this trial. We learned also that to reach a negative MRD at post-induction is very important in terms of PFS and it shows to us how it is important to optimise this induction phase of treatment in myeloma.
At the following timepoints we saw that clearly the patients that reached the highest rates of MRD negativity at 10-5 but also 10-6 are those who have dara-VTd at induction consolidation and daratumumab maintenance. It allows the better PFS including in what we called high risk patients at this time but now maybe it could change. But at this time we have deletion 17p and t(4;14) and with daratumumab it’s better.
What do you think will be the clinical impact of this study?
It’s difficult for me to say because I’m a biologist so I don’t treat the patients. But what I can say is that clearly the incorporation of an anti-CD38 in the triplet is mandatory now. It’s clearly a benefit in terms of PFS and overall survival. Another important thing is the role of the maintenance in the treatment. Here we had a comparison between daratumumab alone maintenance and observation. We saw other clinical trials such as PERSEUS and [??] when daratumumab was combined with lenalidomide versus lenalidomide alone and definitely we feel that this intensive maintenance leads to a better survival, maybe in particular for high risk patients.
