Case 1: Transplant Eligibility in Myeloma

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARDAjai Chari, MD:In terms of the initial indications for treatment and selection of treatment, what do you think? Is this one of our usual historical dichotomies—transplant-eligible or not?

Nina Shah, MD:That’s always an interesting question, especially for a 74-year-old patient. People used to say, “For a patient over age 70 or over age 65, they’re definitely transplant-ineligible.” Now we know that’s not true. Age is just a number. It doesn’t necessarily correlate directly with functional status. Right now, this person has an ECOG [Eastern Cooperative Oncology Group] performance status of 1, but that actually could get better. If he gets therapy, gets better, and if his anemia improves, he may become an ECOG of 0. Indications for treatment, in this patient, right now surround anemia, but he probably needs a PET scan or at least a whole-body CT in contrast to see if there are other bony lesions that would explain some of the hypercalcemia, etcetera. I think he’ll make criteria, and he does for treatment.

After considering treatment, when thinking about transplant, it would be based on his performance status. Being age 74 would not be the limitation. I actually do offer transplant to my older patients, even through age 75. I’ve actually gone higher. Sometimes I’ll decrease the melphalan dose from 200 mg/m²to 140 mg/m², but I’ve found that they generally tolerate it well. This allows them to get a certain number of cycles of therapy and then get the transplant and proceed to maintenance, which we’ll talk about later. I think this person should at least be considered for transplant. Just because of age, he shouldn’t be denied. He should definitely be referred to someone to make that decision.

Ajai Chari, MD:Part of the evolving change in oncology is not just in looking at age. We have the great frailty indices in myeloma as well.

Nina Shah, MD:Yes.

Ajai Chari, MD:You alluded to a few cycles. Let’s say that we’re postponing the definitive decision for transplant. What would your preferred initial therapy be for this gentleman?

Nina Shah, MD:As demonstrated by the ALCYONE trial, if you were saying that this person was transplant-ineligible, you could give them daratumumab/VMP [bortezomib, melphalan, and prednisone]. In the United States, this is a bit difficult to swallow because we rarely use VMP. For that reason, there may be some hesitation to do that. But, you could consider giving a triplet regimen to this patient for somewhere between 4 and 6 cycles, depending on tolerance. You really have a multitude of options. You could consider the RVd [lenalidomide, bortezomib, and dexamethasone]-lite regimen, which was fairly successful in the data that you’ve produced. Even CyBorD [cyclophosphamide, bortezomib, and dexamethasone] is reasonable. That is very well tolerated in this age group. I don’t know if we can really extend the daratumumab component from the VMP to the other triplets yet. That remains to be seen.

Ajai Chari, MD:Ola, what would you do?

C. Ola Landgren, MD, PhD:Well, I think Nina kind of covered it all here, so I’ll try to add some nuances. The patient’s age does not preclude transplant as an option. You could also take the other approach and say that with all of the new drugs that we have, you could actually drive down the disease very deeply. Maybe transplant doesn’t have to be given. Putting those 2 pieces together, from a practical point of view, if the patient is not really thinking about a transplant upfront, is a 74-year-old patient really a patient for whom you’d think about doing a delayed transplant? Probably not. I think that’s an important discussion to have. If the transplant is going to be given, maybe now is the time. If it’s not going to be given now, there is probably not any reason to think about collection of stem cells. If the relapse comes at age 80, you’re probably not going to offer the transplant. That’s an important discussion to have with the patient.

I would think about using RVd-lite. You went over that very carefully and it’s a good option. CyBorD is another good option. There is quite limited, detailed information in the literature comparing RVd versus CyBorD. A French study showed that the IMiD [immunomodulatory drug] gives a deeper response, and that’s the clinical gut feeling that I have as well. If you’re thinking of RVd-lite, the less of therapy compared to CyBorD, I think they could both be considered. If there is a little bit of kidney failure, maybe you could argue pro-CyBorD.

So, you have CyBorD. You have RVd-lite. I think they’re both very valid options. You could also think of KRd [carfilzomib, lenalidomide, and dexamethasone]. I actually use this regimen in a lot of patients and I know you have done this as well. I just completed therapy for an 80-year-old patient in my clinic. This patient got 8 cycles of KRd. With MRD [minimal residual disease]-negativity, that went very well. I’ve treated a lot of older patients with KRd. It’s a very powerful regimen. This patient has a t(14;16) translocation. Why would you not offer this patient, who’s 74-years-old, the best therapy that you have? I think you could make a case for any of these regimens. I would have the discussion with the patient. I would go over the pros and cons and make the decision, together, with my patient.

Ajai Chari, MD:This is a great discussion on a 74-year-old patient with symptomatic myeloma. We have established clonality by blood and marrow testing. Luckily, we have a lot of choices. We don’t necessarily have to make a final transplant decision when we first meet the patient. There’s an important element of response and tolerance to other therapy. It’s good to have options. I think this was a great discussion.

My take on this 74-year-old—he clearly has symptomatic disease and benefits from therapy. I think the evidence has shown that we can do a lot of different things. We have a lot of options, but I would probably start with either RVd or CyBorD. Sometimes, for someone with borderline renal function, I like to start with CyBorD so that you can improve the renal function. Then, I come in with lenalidomide on the second cycle. I am confident that the dosing is appropriate for the whole cycle. We can wait to see the response to 4 cycles of therapy. If the patient tolerates a therapy well and has no toxicity, do we need the transplant? However, if they have intolerance or get a suboptimal response, do we definitely consider transplant? So, I don’t think it’s a binary decision at the beginning—yes or no, and forever—but, it’s nice to preserve that option.

The future studies that have data coming out will be really exciting for myeloma patients. From the SWOG S0777 study, we’ve already seen that RVd was superior to Rd. The other study showed that VMP was better than MP [melphalan and prednisone]. So, we have 2 studies that show that triplet regimens are better, with the caveat being that this was explored in older patients. Another option that’s going to be coming out is Rd [lenalidomide and dexamethasone] versus daratumumab/Rd. It will be interesting to see how that pans out. There is a lot of excitement given the safety profile of daratumumab with other drugs. And, of course, we then move on to quadruplet regimens. With daratumumab/VMP showing superiority to VMP, the question will be, daratumumab/VRd versus VRd, for those of us who like the VRd backbone here in the United States. The GRIFFIN study will hopefully shed some light on that. This is a phase II study with a sizable number of patients. So, I think a lot of exciting data will be coming out in the near future. With that, thank you for your time. This discussion was very interesting.

Transcript edited for clarity.