IMS 2025 | PRO and safety in patients with NDMM achieving MRD negativity in the PERSEUS and CEPHEUS trials

As you know, it is well established that MRD negativity is associated with prolonged survival, and this has translated into a new endpoint for accelerated conditional drug approval. But regulators require evidence that achieving the deepest level of response, in this case defined as MRD-negative, does not occur at the cost of an increase in the rate of adverse events or a patient’s state of deterioration. In order to answer this question, we decided to focus on two recent trials. Two recent trials that have generated a new standard of care by comparing data BRD versus VRD. As you know, in these two trials, MRD was included, what I think is very interesting, as a primary or secondary endpoint. In addition, in both trials, a very rigorous evaluation of the PRO, patient-reported outcomes, was performed using the EORTC questionnaire, and treatment-emergent adverse events were also very rigorously evaluated using the NCI version 5 scale. In this presentation, I will update the information showing that quadruplets are associated with superior MRD-negative rates. But interestingly, we will update that patients achieving MRD negativity have longer PFS and longer treatment duration in the quadruplet arm as compared with the triplet. And because of the difference in treatment duration between the MRD-negative and the MRD-positive patients, we assess the exposure-adjusted safety outcome per 100 patient-years. And focusing on the results regarding treatment adverse events, both in the Daratumumab and in the VRD, the overall frequency of treatment adverse events consistently favors patients who achieve MRD negativity. And this applies not only to overall frequency, what is more important when you focus on serious adverse events or adverse events that lead to discontinuation or death, or you focus on the rate of infection, in both studies, clearly favors patients who achieve MRD negativity. In addition, regarding the patient-reported outcome, it was similar for patients in the Dara-VRD and the VRD who achieved MRD negativity versus the MRD-positive patients. In fact, it was slightly better, the EORTC score in the MRD-negative patients. Then, I think in this study, it is rather important because we are showing for the first time that achievement of MRD negativity does not only improve survival, but is also associated with favorable PRO and exposure-adjusted safety outcomes versus the MRD-positive patients treated, and this is important, with the new current standard of care that are going to be particularly the quadruplets. And I think overall, this data will help reassure physicians that the pursuit of MRD negativity in patients with newly diagnosed disease does not adversely impact on the safety outcome of our patients.

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