Adding Daratumumab to VRd Boosts MRD Negativity in Transplant-Ineligible Myeloma

In an analysis of the phase III CEPHEUS trial presented at the American Society of Hematology annual meeting, adding daratumumab (Darzalex) to bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) significantly improved rates of minimal residual disease (MRD)-negativity and progression-free survival in newly diagnosed multiple myeloma patients ineligible for stem cell transplant.

In this exclusive MedPage Today video, Sonja Zweegman, MD, PhD, of Amsterdam University Medical Center in the Netherlands, discusses the transformative impact of daratumumab-augmented quadruple therapy on MRD negativity and progression-free survival in myeloma treatment.

Following is a transcript of her remarks:

The CEPHEUS trial is a trial for newly diagnosed multiple myeloma patients who are not eligible for stem cell transplantation, or in whom a transplant was deferred. And 395 patients were randomized either between bortezomib, lenalidomide, and dexamethasone, eight cycles, followed by [lenalidomide and dexamethasone; Rd] until progression, or daratumumab added to VRd [D-VRd], and then continuous therapy with [daratumumab]-Rd until progression.

We presented already the impact of the addition of daratumumab on progression-free survival, so that led to a 43% risk reduction in progression or death. And at 54 months with D-VRd, almost 70% of the patients were still without progression or death.

And so now we presented a more in-depth analysis on the minimal residual disease data, minimal residual disease. So the MRD-negative CR [complete response] rate actually was the primary endpoint of the study, and we saw a 50% increase in MRD-negative CR rate after the addition of daratumumab to the drug regimen.

And that also accounts not only for 10^-5, but also for the sensitivity level of 10^-6. And when you look to the cumulative incidence rate of MRD, you see that with the addition of daratumumab, it led to a faster MRD negativity. The MRD negativity levels were higher on all time points. And also the difference between the arms between the MRD-negativity rates increased up to 3 years.

When you reach 10^-6 MRD-negativity CR rate with D-VRd, that led really to a superior progression-free survival. So then at 54 months, more than 85% of the patients were free of progression and death. And so that indicates that reaching MRD-negative CR is a key goal in the treatment of multiple myeloma. And with [daratumumab]-VRd, the rate of reaching MRD-negative CR rate is much higher than with only VRd. So that paves the way for quadruple therapy also in patients who are not eligible for a stem cell transplantation.

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