A 54-Year-Old Woman With Multiple Myeloma - Episode 3

Dara-KRd in NDMM: Results From the MASTER Study

Shifting his focus to the MASTER study in newly diagnosed multiple myeloma, Ajay K. Nooka, MD, MPH, FACP, highlights the role of daratumumab with KRd.


Ajay K. Nooka, MD, MPH, FACP: Dara [daratumumab (Darzalex)]-KRd [carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone] is used in the MASTER trial. It’s a single-arm trial. It did not have a comparative partner compassion arm to assess the benefit of daratumumab plus KRd versus KRd.

The MASTER trial evaluated 123 patients to receive daratumumab plus KRd as sequential boxes of treatments. So if you think about each box having 4 cycles of daratumumab plus KRd, all patients would receive the first induction treatment with 4 cycles of daratumumab plus KRd, and patients would receive an MRD [minimal residual disease] negativity soon after completing the induction treatment.

Patients would receive a transplant then, and patients would receive an MRD negative testing after transplant. And patients would receive the next box of treatment as 4 cycles of daratumumab plus KRd consolidation. And after every 4 cycles, which is after each box, an MRD test is being done.

The second part of the question that [the] MASTER trial has asked was, can we stop off the treatment among these patients who have achieved an MRD negativity? So, if you look [at] the entire context of the trial, the first question of daratumumab plus KRd, this efficacy was phenomenal.

You could see [that] 90% of patients after the completion of [the] induction treatment achieved close to a VGPR [very good partial response], and these responses only deepen after transplants. Seventy percent of the patients achieved a complete response.

Now, in the long run, again, the PFS [progression-free survival], as well as the overall survival in this study is very different than the previous studies that we discussed because there is a portion of patients that are coming off the treatment in this specific trial, which in my opinion, is not the right way to do [it]. And we are using a sharp demand point to make a treatment decision at this point in time.

Time will tell us in the long run who should not be stopping the treatment. We’re already seeing evidence of this hurting a group of patients, at least the high-risk patients, where patients tend to have the disease relapse during the period of maintenance. Of course, these patients are being treated again, but [it] may not be the right approach.

We’ve said it time and again, continuous treatment helps to keep the disease under control in multiple myeloma. And the point I would take home from this study is [that] Dara [daratumumab]-KRd is a great regimen, and the induction setting is able to deliver those responses that we are looking for.

But the point I’m not too enthused about is stopping those treatments when you achieve a short-demand goal, like an MRD-negative case.

Transcript edited for clarity.