Sequencing Novel Therapies in Multiple Myeloma Treatment Algorithms

Saad Z. Usmani, MD: We come to the last questions we have. As you consider treatment options, PI [proteasome inhibitor]–based vs IMiD [immunomodulatory imide drug]–based on options, if this patient had discontinued maintenance after a year for any reason and had been off treatment for a year, would you still consider going back to an option based on IMiD? How would you distinguish that? There are no clinical trial data. What would influence your decision making?

Sham Mailankody, MD: I would probably still favor a non-IMiD regimen in someone who relapsed within 1 or 1.5 years of stopping treatment, because on average one would expect a bit longer duration of remission with a transplant more or less the maintenance of old data. Within 1 year of maintenance, in a patient with an MRD strict complete response [minimal residual disease] negativity, you have the disease that comes back within a year without any maintenance. That worries me. This does not mean that this patient cannot switch back to IMiDs or lenalidomide [Revlimid] or try different combinations in the future. But as a first step, unless there are compelling reasons not to choose them, I would go for a proteasome inhibitor and a CD38 combo.

Saad Z. Usmani, MD: Do you feel different?

Neha Korde, MD: No. I like this answer.

Saad Z. Usmani, MD: It’s perfect. I have a question that we don’t have an answer to, but I want to get an idea from you. We talked about how often daratumumab is used in the first line for our patients and how safe it is for transplant-eligible patients. We haven’t decided if we’ll continue it as maintenance for transplant-eligible patients, but the idea is that we’ll probably do it for a set amount of time for some patients. Then, for patients not eligible for transplant, we said the data from the MAIA study was super impressive. We use this data to treat our patients, and many of these patients will continue to use daratumumab as part of ongoing treatment, such as in the MAIA study.

With that in mind, how do you think the landscape will change and the choices will change when patients present for the first relapse? If you have someone who is refractory to anti-CD38, what would be our choices? Instead of lenalidomide maintenance therapy, what would happen if this patient received daratumumab-lenalidomide maintenance therapy?

Neha Korde, MD: This is where we really need testing, isn’t it? This is where we see the various combos come to the fore and things get mixed up a bit. Obviously, as BCMAs are progressing well with clinical trials, hopefully we will be able to fill in some of these questions and gaps with either CAR. [chimeric antigen receptor] T or bispecific cells. Especially with these new targets, this is where we’ll likely see more data as anti-CD38s come to the fore.

Urvi Shah, MD: I definitely agree. In terms of standard care options, Cytoxan [cyclophosphamide] is a good option when combined with carfilzomib [Kyprolis] if they had daratumumab–RVd [lenalidomide, bortezomib, dexamethasone] early, or pomalidomide [Pomalyst] with Cytoxane. Some of these drugs could be used.

Saad Z. Usmani, MD: Even some of the newer and smaller molecules, right?

Urvi Shah, MD: Yeah.

Saad Z. Usmani, MD: We have the iberdomide, and we have the CC-480 coming on the pike. Some other upcoming options might also become possibilities. We kept coming back to the MRD-negativity piece. If you maintained MRD negativity as an endpoint where you stop treatment, you will have patients who will get a fairly reasonable drug-free interval. These patients are exposed to these classes of drugs, but will not be refractory. You can also potentially recycle some of these action mechanics.

Sham Mailankody, MD: Along those lines, if you look at all the studies that we’ve talked about, the control arms of studies with 3-drug combinations, at 3 years for something like the GRIFFIN study, 80%+ of patients, even with just RVd [lenalidomide, bortezomib, dexamethasone] and 2 years of maintenance—are progression-free. The scenario we just discussed is fortunately not very common due to the advances we have made with treatments. Obviously, we remember our patients who fall into this category, whether they are quadruplets or doublets, and then relapse in 6 to 12 months. But the good news with myeloma, no matter what effective treatment you choose, is that the overwhelming majority can go 3-4 years without disease progression.

Transcript edited for clarity.

Sharon D. Cole