Paula Rodríguez-Otero, MD, University of Navarra, Navarra, Spain, highlights MRD results from the phase 3 PERSEUS trial. This research was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Rodríguez-Otero and study authors found that results support the use of daratumumab plus bortezomib, lenalidomide and dexamethasone (D-VRD) induction and consolidation, followed by daratumumab in combination with lenalidomide (DR) maintenance, as a standard of care treatment for transplant-eligible patients with newly diagnosed multiple myeloma (MM).

Transcript:

Hello, my name is Paula Rodríguez-Otero, I am a hematologist working at the University of Navarra in Pamplona, Spain. I am here at ASCO Congress 2024, so I am very happy to be here with you. I am going to present the data from the MRD analysis of the Perseus phase 3 randomized study.

Perseus is a phase 3, randomized, multicenter, open-label study that enrolled transplant -eligible, newly diagnosed multiple myeloma patients with age between 18 and 70 years. They were randomized 1-to 1 to receive VRD induction, followed by single transplant and VRD consolidation, and then lenalidomide maintenance until progression. In the experimental arm, patients were treated with daratumumab in combination with VRD, 4 induction cycles, single transplant, 2 consolidation cycles of D-VRD, and then daratumumab in combination with lenalidomide (DR) maintenance for up to 2 years.

Then there was a response-adapted approach and patients that were MRD positive with a minimum of 2 years of maintenance, they continue on DR until disease progression, and patients that achieve MRD negativity that was sustained for at least 1 year, they could stop daratumumab and they continue lenalidomide until disease progression.

In this congress we are going to present the MRD data and more data regarding the maintenance phase. As it was presented in the ASH 2023 meeting, we know that D-VRD induction consolidation and DR maintenance was associated with a significant increase in progression-free survival, and that responses were also higher and more deep in the D-VRD-containing arm. Importantly, when we look at the maintenance phase, responses clearly deepened over time, and this deepening of the responses was greater in the daratumumab-containing arm as compared to the VRD. For example, a complete response rate at the end of consolidation was 44% and increased significantly up to 87% during the maintenance phase with the treatment of datatumumab plus lenalidomide.

Likewise, MRD negativity, both 10 to the minus 5 and 10 to the minus 6, also increased over time during the maintenance phase and was higher for patients treated in the daratumumab-containing arm, as compared to VRD. Importantly, as well, sustained MRD negativity, both at 12 months or longer or also at 18 months or longer, was higher in the daratumumab-containing arm as compared to the VRD, both at the threshold of 10 to the minus 5 and, more importantly, at the threshold of 10 to the minus 6.

In the subgroup analysis, both for MRD and also for sustained MRD, all subgroups favor the daratumumab-containing arm, including patients with 65-year-older or high-risk cytogenetic abnormalities, both at 10 to the minus 5 and 10 to the minus 6 threshold. There is also an analysis focusing on high-risk patients that were defined in the study as patients either harboring deletion 17p, trans location 4;14 or trans location 14;16 and we do see the same signal—so patients treated with daratumumab VRD induction consolidation and DR maintenance had a higher rate of MRD negativity, both 10 to the minus 5 and importantly also 10 to the minus 6, and also a higher proportion of sustained MRD for patients with high-risk disease treated with daratumumab combination. This was associated with a prolonged progression -free survival.

This data shows that first there is a deepening of the responses throughout treatment, and most importantly during the maintenance phase that patients treated with daratumumab VRD induction consolidation and DR maintenance have a higher rate of MRD negativity, a higher proportion of sustained MRD negativity, and 1 important piece of information that will also be discussed is that a higher proportion of patients that were still MRD positive after consolidation, they were able to convert to MRD negativity and to sustain MRD negativity in the daratumumab-containing arm, as compared to the VRD plus [lenalidomide] alone arm.

All this data supports a D-VRD induction consolidation followed by DR maintenance as a new standard of care for the treatment of transplant-eligible newly diagnosed myeloma patients.

 Source:

Rodríguez-Otero P, Moreau P, Dimopoulos MA, et al. Daratumumab (DARA) + bortezomib/lenalidomide/dexamethasone (VRd) in transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM): Analysis of minimal residual disease (MRD) in the PERSEUS trial. Presented at the ASCO Annual Meeting. May 31–June 4, 2024; Chicago, IL. Abstract 7502