Treatment Rationale for Using Triplets vs Quadruplets in Multiple Myeloma

CASE SUMMARY

At a live virtual event, Alfred L. Garfall, MD, discussed the case of a 54-year-old woman diagnosed with Revised-International Staging System stage II/III IgG-kappa multiple myeloma who was transplant eligible. While reviewing this case, the clinicians discussed the wider role of quadruplet and triplet therapy regimens, like bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd), in patients like this after transplant. They also highlighted the role transplanters play in helping them to reach these treatment decisions.

ALFRED GARFALL, MD: Maybe we could talk a little bit about how folks decide between quadruplet and triplet regimens, and what influences your decision-making there.

Alfred L. Garfall, MD

Director, Autologous Hematopoietic Stem Cell Transplantation

Assistant Professor of Medicine

Hospital of the University of Pennsylvania

Philadelphia, PA

BERNARD KULPER, MD: I think whether you use a triplet or a quadruplet [regimen], to some degree, depends on if [the patient] is transplant eligible or not. Then, if they are transplant eligible, I would leave the decision of the regimen up to the transplant team and follow their lead. Otherwise, I would probably use one of the triplet regimens.

GARFALL: So, you would have the patient see the transplant center before starting systemic therapy?

KULPER: That would be correct, and then see what [that team] want to do. If they consider a patient transplant eligible, then whatever regimen they're comfortable with using I would go along with their decision, because ultimately, they're the transplanters.

GARFALL: Is there a perception among [all of you] that 1 of these regimens might be friendly in terms of the potential [for the patient to go] on to stem cell transplant over any other regimen? Or maybe we could hear from somebody who prefers the triplet regimen, what was the thinking behind the triplet vs the quadruplet regimen for this particular patient?

JOSE SILVA, MD: I [would] choose the triplet, mostly because of our institutional built systems. I think daratumumab [Darzalex] is eventually going to come and be part of the front line. However, unless we are guided by the transplant service to do it up front, we'll reserve it for later.

GARFALL: What has been everyone's experience using quadruplets and triplets for different patients? Quadruplets are something that we've been using over the last few years, [while] VRd was the standard. So, what has been the experience with quadruplets? [Is there] anything more complicated about it? Any more toxicity? Is the response better? What's the experience out there comparing those 2 approaches?

NEHA CHAWLA, MD: I've used the quadruplets, and I have not experienced much in the way of added toxicity with daratumumab. The only thing [that has had some additional toxicity], I think, is the steroids. After a few cycles, I tend to decrease the steroids, especially for diabetic patients, or you get a lot of weight gain, but I think it's quite well tolerated [overall].

BUSHRA HAQ, MD: I agree. I haven't seen much additional toxicity with adding daratumumab, and [I have seen] better efficacy.

GURPRATAAP SANDHU, MD: I agree, and I've used the triplet and quadruplet [regimens]. I've typically started off with VRd, [and then] I refer these patients to the transplanter, and if they think [the patient has] high-risk multiple myeloma, they ask me to add daratumumab on top of it.

SABRINA MARTYR, MD: I've only used a quadruplet regimen in 1 or 2 situations, but in both of those cases, those were patients with high-risk cytogenetics. I haven't used the acute versions, I mostly had experience with the [intravenous therapy], but so far it has been well tolerated. My only issue is that I have sent patients to 2 different transplant centers, and when they come back, the recommendation for what maintenance should be was slightly different [between them]. One center kept the daratumumab [recommendation] and the other did not.

GARFALL: I think there is some uncertainty about that, and that question is the subject of a big cooperative group study, SWOG1803 [DRAMMATIC; NCT04071457], which is looking at patients after randomly assigning them to daratumumab plus lenalidomide vs standard lenalidomide maintenance after transplant.¹

It is an all comers trial in terms of induction, so many of those patients on that trial will have gotten daratumumab pre-transplant, but many will have not, and so we'll get to see [the responses] over time. I know that is a big trial, [at an estimated enrollment of] 1100 patients, and it’s powered for overall survival. We're going to be waiting a while for the results, but I think it's an important study to address that question where there's a lot of uncertainty.

Reference:

MD Anderson Cancer Center. SWOG1803: Phase III Study of Daratumumab/rHUPH20 (NSC-810307) + Lenalidomide or Lenalidomide as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients with Multiple Myeloma Using Minimal Residual Disease to Direct Therapy Duration (DRAMMATIC). 2023. Accessed June 13, 2023. https://www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2020-0062.html