ASH 2023 | The PERSEUS trial: primary results of D-VRd vs VRd in newly diagnosed, transplant eligible MM
Pieter Sonneveld, MD, PhD, Erasmus MC, Rotterdam, The Netherlands, discusses the protocol and the primary results of the ongoing Phase III PERSEUS trial (NCT03710603) comparing subcutaneous daratumumab (D) with VRd (bortezomib, lenalidomide (R) and dexamethasone) followed by D-R maintenance to VRd with R maintenance in patients with newly diagnosed multiple myeloma (MM) who are eligible for an autologous stem cell transplant (autoSCT). At a median follow-up of almost four years, the primary endpoint was met, with higher progression-free survival (PFS) in the D-VRd arm. During maintenance, a measurable residual disease (MRD)-guided approach was used, allowing two thirds of patients to stop receiving daratumumab. Dr Sonneveld highlights that the addition of daratumumab to the VRd regimen benefits patients and he hopes that this treatment approach will be approved as the standard of care globally. This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (edited for clarity)
So the PERSEUS trial was designed to test the addition of daratumumab, which is an anti-myeloma targeting antibody, added to standard therapy in patients that were eligible for autologous transplant. And we added daratumumab for induction, for consolidation therapy, but also for maintenance. And it is a Phase III trial, the primary endpoint being progression-free survival and key secondary endpoints are minimal residual disease...
So the PERSEUS trial was designed to test the addition of daratumumab, which is an anti-myeloma targeting antibody, added to standard therapy in patients that were eligible for autologous transplant. And we added daratumumab for induction, for consolidation therapy, but also for maintenance. And it is a Phase III trial, the primary endpoint being progression-free survival and key secondary endpoints are minimal residual disease. The trial was performed in, as I said, in countries across Europe and Australia. A total of 700 patients were included, and this is the first primary analysis at the median follow-up of almost four years.
So the results clearly show that the primary endpoint was met, and the hazard ratio for progression-free survival was 0.42, which is unprecedented in multiple myeloma. Also, at four years, the PFS in the daratumumab combination was 84% against 67% in the non-dara treated patients.
So important here is that daratumumab was given subcutaneously, which is much better tolerated by the patients and [results in] less infusion reactions, and also at the four weekly schedule. Then, it was continued into maintenance treatment and in the maintenance patients that had a CR for more than two years and also accomplished MRD negativity for at least a year, could stop daratumumab, so their treatment was reduced to only lenalidomide until progression. And this worked very well; two-thirds of the patients were able to accomplish this. And that is important because patients do not have to come to the hospital every month and the subjective tolerability is perfect.
So in this trial, we have no safety issues. Patients are, of course, ongoing. We must wait for longer follow-up to say anything about median PFS or OS, overall survival, but that will come in the future. But the overall conclusion is that patients really benefit from this treatment, and we expect that this is going to be the standard of care in Europe and Australia, and hopefully also in other parts of the world, once the regulatory authorities have approved this.
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Disclosures
Advisory Board: Pfizer, Celgene, Janssen, Amgen, Karyopharm, Bristol Myers Squibb
Research Funding: Celgene, Janssen, Amgen, Karyopharm, Bristol Myers Squibb
Dr Sonneveld is currently employed at the Erasmus Medical Center.
