Triplet or Quadruplet Therapy in Transplant-Ineligible NDMM

In the context of transplant-ineligible newly diagnosed multiple myeloma, Saad Usmani, MD, considers the role of triplet versus quadruplet therapy.


Saad Z. Usmani, MD: In the United States, for transplant-ineligible patients, the 2 regimens that we are utilizing right now are RVd-lite [modified lenalidomide, bortezomib, and dexamethasone] and DRd, or daratumumab, lenalidomide, dexamethasone. All of us are familiar with RVd and the RVd-lite regimen, which is a dose attenuated weekly regimen that was developed by doctors Betsy O’Donnell, [MD,] and Noopur Raje, [MD,] at Massachusetts General Hospital. Those are the 2 regimens that we typically utilize. It’s triplets. For daratumumab, lenalidomide, dexamethasone, or DRd, the data come from the randomized phase 3 trial MAIA, which had demonstrated better overall response rate, PFS [progression-free survival], MRD [minimal residual disease] negativity, and now even overall survival [OS] benefit in favor of the 3-drug combination.

Then the key question about whether a quadruplet also makes sense for this patient population is being examined in several clinical trials. There’s a study called CEPHEUS, which is comparing daratumumab-RVd with RVd for transplant-ineligible patients. It’s a randomized phase 3 trial, and the results are not in the public domain; it’s an ongoing study. However, at ASH [American Society of Hematology annual meeting], there was a randomized phase 2 study that was reported by our Australian colleagues that looked at the use of CyBorD [cyclophosphamide, bortezomib, dexamethasone], also known as VCd, as standard of care compared with additional daratumumab to VCd or CyBorD. This is a small study, 129 patients were randomized to the 2 arms. The study also had continuation of daratumumab as part of maintenance for patients. What was important to see in this trial was that the PFS benefit favored the 4-drug regimen compared to the 3-drug regimen in terms of median PFS. If you look by age group, whether patients were younger than 75, or equal to or older than 75, there didn’t appear to be any differences either.

The colleagues concluded that adding daratumumab to the VCd regimen improves responses and helps them achieve MRD negativity. From an overall study standpoint, the PFS benefit was seen with the induction regimen. Now for daratumumab in the maintenance setting, they do not have enough long-term follow-up to see whether that makes sense. The median OS was reported at 2 years as a percentage, and it was 88%, and there weren’t any differences between the 2 arms. Again, we don’t have long-term follow-up on this study. They are interesting data, I would probably keep a closer eye on this, but it’ll likely not change my practice. I would still continue to utilize either RVd or DRd as part of my standard of care practice.

Transcript edited for clarity.

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