EHA 2021 | Cassiopeia: analysis of daratumumab maintenance for myeloma
Philippe Moreau, MD, Nantes University Hospital, Nantes, France, gives an update on the Phase III Cassiopeia study (NCT02541383) of daratumumab maintenance therapy in patients with newly diagnosed multiple myeloma who undergo autologous stem cell transplantation (ASCT). Prof. Moreau reports that in part 1 of the study, comparison of bortezomib, thalidomide and dexamethasone (VTd) with daratumumab versus without daratumumab demonstrated improved response rate and progression free survival with the addition of daratumumab to VTd. In part 2 of the study, patients were rerandomized to receive either maintenance with daratumumab monotherapy versus observation. Prof. Moreau reports that study met its primary endpoint with a significant improvement in progression free survival (6.7 months versus not reached) with daratumumab maintenance. Prof. Moreau also reports that this benefit was most prominent in patients who received VTd upfront without daratumumab, and that measurable residual disease negativity was highest in patients who received VTd plus daratumumab and daratumumab maintenance. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.
Transcript (edited for clarity)
So, the Cassiopeia study is a randomized Phase III study looking at the impact of daratumumab in patients newly diagnosed, treated with autologous stem cell transplantation. So, in part one of the study, we looked at VTd versus VTd plus daratumumab and we showed that the response rates and the progression-free survival was in favor of the dara-VTd arm with a significant improvement in terms of PFS...
So, the Cassiopeia study is a randomized Phase III study looking at the impact of daratumumab in patients newly diagnosed, treated with autologous stem cell transplantation. So, in part one of the study, we looked at VTd versus VTd plus daratumumab and we showed that the response rates and the progression-free survival was in favor of the dara-VTd arm with a significant improvement in terms of PFS. And that was the basis of the approval of dara-VTd for young patients treated with stem cell transplantation.
And, in the part two of the study, patients were re-randomized to maintenance with daratumumab single agent, 16 milligrams per kg IV, every eight weeks for two years maximum versus no maintenance, versus observation. When we designed the Cassiopeia study, lenalidomide, that is now the standard of care for maintenance, was not approved. So, that’s why we decided to have an observation control arm.
In the part two of the study, 886 patients were re-randomized to dara maintenance versus no dara versus observation only. There was no difference when looking at patients’ characteristics for this second randomization and the study met its primary endpoint with a median follow-up of three years, from second randomization. We have a significant improvement in progression-free survival versus observation with a hazard ratio of 0.53. And the median PFS in the observation arm is 46.7 months versus not reached with daratumumab.
But when we looked at pre-specified subgroups, we immediately see that the patient group that is benefiting from dara maintenance is the one who did receive VDt upfront. And when you are receiving dara-VTd upfront, there is no benefit of dara maintenance, indicating that it is important to receive daratumumab in the maintenance when you are not treated upfront with dara and receiving only a triplet combination.
There is a strong interaction between induction and maintenance. We were able also to show that daratumumab maintenance is increasing the depth of response, is extending time to progression, and we are currently looking at minimal residual disease and the rate of MRD negativity was higher, in fact, for those patients who are treated with dara-VTd upfront and dara maintenance.
So, we need now to have a long follow-up, a longer follow-up to look at PFS2. Right now, we are seeing that there are some differences, the curves in terms of PFS2 are starting now to diverge. We need a longer follow-up to see the exact impact of dara maintenance. Interestingly as well, we did an update data analysis from first randomization, and we did confirm the benefit of dara-VTd versus VTd induction and consolidation.
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