Myeloma Maintenance Based on AURIGA Study Insights

Ashraf Badros, MB, ChB, professor at the University of Maryland School of Medicine, director of the Multiple Myeloma Service, and vice chair of the Clinical Research Committee for the Program in Oncology, is attending the 21st annual International Myeloma Society's conference in Rio de Janeiro, Brazil, between September 25 to 28.

Badros discussed the AURIGA study in which daratumumab is combined with lenalidomide and compared with lenalidomide alone as a maintenance therapy in patients with newly diagnosed multiple myeloma following transplants. He emphasized the need for future trials that explore the optimal duration of maintenance.

This transcript has been lightly edited for clarity.

Transcript

How do the results of the AURIGA study compare with other studies that have evaluated maintenance therapy for patients with multiple myeloma after autologous stem cell transplant (ASCT)?

Since that concept [AURIGA trial] has been accepted and lenalidomide was introduced, we really have a trial that does not include lenalidomide as maintenance. The exception to that is the trial from Spain called the CASSIOPEIA trial. This particular trial, after transplant, randomized patients between observation and daratumumab.

Again, the trial is not a very clean trial because the induction arm included daratumumab for patients that went on to receive daratumumab for maintenance vs no maintenance. The induction treatment was also different than what we use in the US, including something called VTd—Velcade [bortezomib], thalidomide, dexamethasone—but the trial supports a role for daratumumab in maintenance in that setting, showing improvement in responses in MRD [minimal residual disease] negativity and in PFS [progression-free survival].

The question was, "Which group of patients benefited the most when they randomized patients after transplant?" It looks like patients that did not get daratumumab upfront had the most benefit. The GRIFFIN trial and the PERSEUS trial, where patients received daratumumab upfront followed by daratumumab maintenance, showed clear benefit for adding daratumumab in the maintenance setting.

If you look at the PERSEUS trial, at the end of transplant consolidation, about 50% of the patients were MRD negative. After adding daratumumab and lenalidomide maintenance, that benefit improved about 75%.

It's clear that continuous treatment with daratumumab/Revlimib [lenalidomide] improved the response as we continued treatment. I think this is a very evolving area and we are probably not going to have a standard of care for daratumumab/lenalidomide for at least 3 or 4 more years when we have some more trials to give us the answer, but I think the data support using it and support adding it to lenalidomide.

How will the results of the AURIGA study be used to inform future clinical trials in multiple myeloma?

I think the best, the most important trial we're waiting for is a SWOG trial called the DRAMMATIC trial. The DRAMMATIC trial will be a definitive trial and it will address the same question in addition to addressing the duration of time patients will receive treatment.

This particular trial would be very helpful in not only discussing the maintenance we use, but also how long the maintenance is used for, the type of maintenance used, and length of time the patient is on maintenance. Is 3 years enough? Is 4 years enough? Can we make a decision after 2 years if MRD is negative?

Unfortunately, we don't have enough data at the moment. There are some preliminary trials, like the MASTER trial, that try to stop treatment once the patient achieves MRD negativity that was sustained to see if the patient will progress or not.

I think the data are accumulating that we can and maybe should use MRD to guide treatment. That would be the next wave of trials to try to decide if we have very deep responses, if we achieve 10^–5, what do we do with this deep responses? Do we continue or stop treatment? I think that would be a very important point to discuss in the future, trying to understand the role of MRD negativity and guiding therapy. So far, we don't have solid data to tell us when to stop treatment and what to do when they progress or become MRD positive off of treatment.