Triplet and Quadruplet Therapy Options for Patients With Transplant-Eligible NDMM


An overview of triplet and quadruplet induction regimens used for the treatment of patients with transplant-eligible newly diagnosed multiple myeloma.


Ola Landgren, MD, PhD: Dickran, could you introduce the triplet and quadruplet induction regimen options for a patient who’s transplant eligible?

Dickran Kazandjian, MD: For the triplet therapies, usually we think of appropriate regimens as having a proteasome inhibitor and an immunomodulatory drug. That’s VRd [bortezomib, lenalidomide, dexamethasone] or KRd [carfilzomib, lenalidomide, dexamethasone] as the backbone. Although we’ve had pretty good responses up front, we have room to improve. In the era of the monoclonal antibodies, we’ve introduced daratumumab and later isatuximab to both backbones.

Some of the most mature data we have on this is from the GRIFFIN study, which shows that adding the monoclonal antibody improves outcomes to the 3-drug backbone. But some of the initial studies were important, including adding daratumumab to KRd [carfilzomib, lenalidomide, dexamethasone] in the MANHATTAN study. That led the field—it was a single-arm study—to more randomized studies. It’s very exciting because at this point we have studies that are not only using 4 drugs but are also studies like the MASTER trial, which is experimenting on actual de-escalation after getting quadruplet therapy up front.

Ola Landgren, MD, PhD: You bring up a lot of trials. I was going to ask Ben about the MASTER trial and also GMMG-CONCEPT, which comes from the German study group. Could you talk about that, Ben?

Benjamin Diamond, MD: We like both of these trials because they’re pushing the practice forward. With the MASTER trial, we’re experimenting with de-escalation of therapy for appropriate patients. There are the patients who get daratumumab–KRd [carfilzomib, lenalidomide, dexamethasone] for 4 cycles, a transplant, and then a varying number of future consolidation cycles based on MRD [minimal residual disease] testing. If patients have 2 consecutive MRD tests that are negative, they go into a phase called MRD-SURE, which is a treatment-free interval where they can be monitored without further therapy.

There was also enrichment for patients with high-risk cytogenetics or patients with high-risk lesions. The GMMG-CONCEPT study was in the same vein, except only for patients with high-risk disease, which is an underserved population. These are patients who are getting the same combination but swapping out the daratumumab for isatuximab and getting it for 6 cycles. There are 2 arms. There’s either transplant or no transplant with some consolidative isatuximab–KRd [carfilzomib, lenalidomide, dexamethasone] and then maintenance with isatuximab–KR [carfilzomib, lenalidomide]. We’re appropriately trying to improve outcomes for patients in this very high-risk group.

Transcript edited for clarity.

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