Clinical Summary:

• Design/Population: A biomarker analysis of the phase 3 PERSEUS trial evaluated 434 transplant-eligible patients with newly diagnosed multiple myeloma using the IMS/IMWG consensus genomic staging criteria, incorporating FISH and next-generation sequencing to refine high-risk classification.
• Key Outcomes: The updated genomic staging criteria identified a larger high-risk population than older models. Daratumumab plus bortezomib plus lenalidomide and dexamethasone, transplant, and lenalidomide maintenance increased rates of MRD negativity and sustained MRD negativity for at least 1 year in both standard-risk and high-risk patients compared with VRd-based therapy.
• Clinical Relevance: These findings support use of IMS/IMWG genomic staging to better define risk in newly diagnosed multiple myeloma and reinforce daratumumab-VRd–based quadruplet therapy as an effective approach that may mitigate poor prognosis when sustained MRD negativity is achieved.

Luca Bertamini, MD, Erasmus MC Cancer Institute, Rotterdam, Netherlands, discusses results from an analysis of the phase 3 PERSEUS trial evaluating the newly established IMS/IMWG genomic risk classification among transplant-eligible patients with newly diagnosed multiple myeloma. 

Using next-generation sequencing, the new system identified more high-risk patients than traditional criteria and demonstrated that adding daratumumab to bortezomib plus lenalidomide and dexamethasone significantly increased rates of minimal residual disease (MRD) negativity and sustained MRD negativity in both standard- and high-risk groups. 

Transcript:

Hi everyone, my name is Luca Bertamini and I am a physician at Erasmus MC Cancer Institute in Rotterdam, Netherlands. 

I'm really excited to be here at ASCO this year to present results from our recent study where we investigated the prognostic impact of a new risk criteria namely called IMS/IMWG consensus genomic staging in multiple myeloma patients diagnosed with a disease and treated in a large phase 3 randomized trial of the PERSEUS study.

The PERSEUS study is a very well-known study in the field of myeloma as this study just defined the current standard of care for young patients eligible to transplant consisting in the addition of daratumumab to backbone VRd transplant and lenalidomide maintenance. 

In this study, what we did is we really wanted to look into recently established risk classification for myeloma patients. This risk classification was defined by the International Myeloma Society and Working Group in 2025 and includes not only alteration that we find with FISH but also new genetic lesions that we define with next generation sequencing. This is really important because defining the risk of our patients is crucial to understand what's going to be their prognosis and also their treatment.

In this study we analyzed our patients, 434 patients of this large phase 3 study using a targeted NGS panel called UMA panel and what we then looked at was response rates in patients with different risk classification and what were the outcomes of the progression-free survival. Using this panel we could classify our patient's risk and 35% of patients were considered now high risk compared to in the past of the old criteria which define around 22% of patients. There is around 12, 13% more high risk patients we can define.

Moreover, we looked into the prognosis of these patients and what we saw is that first of all, patients with high risk and also standard risk achieved higher rates of deep responses that we measured and defined as MRD negativity when treated with daratumumab. With the daratumumab VRd regimen compared to the VRd regimen. This was true for both patient high risk and standard risk. We also know that achieving this deep MRD negativity is really important to then have a long term good outcome, but one single measurement of this dip response is sometimes not enough.

What we also then did is looking at confirmation of this deep response that we defined as sustained MRD negativity for at least 1 year and patients that achieved this really deep and sustained durable response generally have better outcomes. This was the case also in our study.

Interestingly we saw that patients treated with daratumumab combination achieved higher rates of this sustained MRD negativity both in standard risk and higher risk and this translated into a better outcome. Also what we saw is that if you look after achievement of this very deep response, then your risk doesn't matter anymore. Patients are high risk or standard risk, they do very similar and this is really important because this means that we can abrogate the poor prognosis of these patients' diagnosis with an appropriate treatment and achieving a deep response for a long time.

This really altogether shows how the quadruplets for the addition of daratumumab to VRd is really extremely effective treatment for this patient population for both standard and high risk patient defined with this criteria and really we validated this for the first time in a large phase 3 study showing the importance of risk classification and also how adding more treatments in this case vision of daratumumab really can improve outcome of our patients.

Thank you very much.

Source:

Bertamini L, Terragna C, Bolli N, et al. New IMS/IMWG risk criteria by next-generation sequencing (NGS): Analysis of daratumumab benefit in both high- and standard-risk patients (pts) in the PERSEUS study. Presented at 2026 ASCO Annual Meeting. May 29 - June 3, 2025; Chicago, IL. Abstract 7505.