Deeper MRD Responses Strengthen Shared Decision-Making as Daratumumab Use Expands Across Treatment Phases

Discussing the value of deeper and more durable minimal residual disease (MRD) negativity has become increasingly central to shared decision-making in multiple myeloma, and new findings from the AURIGA trial (NCT03901963) provide clearer grounding for those conversations.

In an interview with Pharmacy Times, Alfred Chung, MD, a hematologist-oncologist at the University of California, San Francisco Health, noted that daratumumab meaningfully increases both MRD-negative and sustained MRD-negative rates with manageable added toxicity, providing patients and caregivers with a stronger rationale for choosing a regimen that improves the odds of achieving deeper remission. As daratumumab use grows in frontline therapy following PERSEUS (NCT03710603), pharmacists and clinicians must also consider how prior anti-CD38 exposure may shape maintenance choices, while ongoing trials such as SWOG S1803 (NCT04071457) aim to refine sequencing and identify when treatment can safely be discontinued.

Q: How do these data inform shared decision-making discussions, particularly when explaining the clinical value of achieving deeper MRD negativity to patients and caregivers?

Alfred Chung, MD: One of the challenges in multiple myeloma is that patients vary in terms of how well they do, so we can't know before the events happen how well people are going to do. So…we try to help patients [by getting them into] the deepest responses they can achieve. We know from the data in AURIGA [NCT03901963] that the addition of daratumumab led to higher rates of MRD negativity and sustained MRD negativity, so it gives a better chance for patients to get into these deeper, deeper remissions.

But we always have to weigh [adverse] effects…treatment efficacy…so we know from AURIGA and other studies with daratumumab that the addition of daratumumab is pretty well tolerated. There may be some small increases in infections, but that's usually very manageable, and the incremental benefit in progression-free survival [PFS], depth of response, [etc,] are higher with the addition of daratumumab. So…we always weigh in [those things] when we discuss with patients. But ultimately, for patients who can tolerate it, we do discuss that adding daratumumab can increase these rates of remission and response.

Q: Considering the contrast between AURIGA and PERSEUS, what role do you think prior exposure to anti-CD38 therapy should play in treatment planning, sequencing, and pharmacotherapy recommendations after ASCT?

Chung: With the results of the PERSEUS trial, a lot of providers are now giving daratumumab up front in the induction therapy, and that's because of the excellent responses that we saw in the PERSEUS trial. Long-term PFS is looking very good there, so I think more and more providers are going to be giving daratumumab up front. And in the PERSEUS trial, the maintenance on that arm did include daratumumab and maintenance for 2 years, with the ability to stop if patients are in sustained MRD negativity for 1 year. That was built into the trial. If providers are following that phase 3 trial and the way it's being given, a lot of patients are going to be on daratumumab-lenalidomide as part of that trial.

In AURIGA, it was different in that patients were not CD38 antibody exposed, so these are patients who didn't have daratumumab before, and the addition of daratumumab was leading to the improved outcomes that we see in that study. But we do need other studies to tease out whether someone has had induction before and whether they do benefit from daratumumab later on in maintenance. And there are studies like the SWOG S1803 DRAMMATIC study, which is currently ongoing and examining this question by randomizing patients who are either receiving daratumumab or daratumumab-lenalidomide, and then conducting another type of MRD-associated randomization to determine whether therapy can be discontinued. There are some who follow PERSEUS, and if you follow PERSEUS, you could do the daratumumab-lenalidomide regardless of initial exposure. But there is debate in the field about that, with studies like CASSIOPEIA [NCT02541383], where maybe the added benefit of daratumumab to lenalidomide may not be as pronounced. But right now, without the results of the SWOG S1803 trial, if we follow the phase 3 data, the most we have right now is from PERSEUS, which did include it. So in general, it's a good maintenance regimen, daratumumab-lenalidomide.