What Is the Optimal Combination for Patients With Multiple Myeloma in Early Relapse?

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Faith E. Davies, Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, reviews how to select the optimal combination of therapeutic agents for patients with multiple myeloma (MM) in early relapse. 

Transcript:

Hi, I'm Faith Davies and I'm one of the attendings at NYU Langone in New York. I've been at the 2022 Lymphoma, Leukemia & Myeloma Congress discussing what we do for patients who are relapsing with multiple myeloma, and particularly concentrating on those early relapses. I think it's incredibly challenging times because we've got so many new drugs that have come through that physicians and patients are confused as to which one's going to be the best treatment for them. 

We spent some time discussing the principles behind what we're trying to achieve in an early relapse. I think that's very much the same as what we're trying to achieve in a newly diagnosed patient. That's a deep remission and certainly with many of our new therapies we're finding that patients can achieve a minimal residual disease (MRD). We're also aiming for that remission to be as long as it possibly can, and with many of the new combinations we're actually managing to keep patients in remission for 2, 3, or even more years.

Thirdly, we're trying to make sure that patients have a good quality of life. We were discussing that, out of the different combinations that are available, we need to choose a member of a different class of drugs to make sure our combination is synergistic. Essentially, we are invariably thinking: should we be using a proteasome inhibitor? Should we be using an [immunomodulary imide drug] IMiD? Should we be using a monoclonal antibody? Or should we be using a targeted therapy? And then probably picking at least 2 or maybe 3 of those drugs from a different class to put together in a synergistic combination. 

When you look at the clinical studies in this area, there's actually many different studies which have shown to be effective. They may have either an IMiD background, a proteasome inhibitor background, or a monoclonal antibody background, but whichever it is, when we're either using 2 or 3 drugs in that combination, essentially what we've been doing is using those drugs until the patient achieves their best response. But many of the studies have been going for patients to continue with their therapy, so not just a fixed-duration, but continuing until either their disease progresses or they have unacceptable side effects. And so often when a patient has achieved their best response, we're going to cut back and move back from 3 drugs to maybe 2 drugs, and then hopefully just leave a patient on 1 drug, which would be their maintenance therapy. 

When we are coming to choose which is the best combination, I think the truthful answer of what we discussed is that there probably isn't a best combination that fits all patients. It's really the best combination for an individual patient. We need to look and say, "Okay, what therapy have they had in the past? Did they get on well with that therapy? Did they tolerate it? Did they have a good response?" And then think about the patient: what comorbidities do they have? Do they have heart issues? Do they have lung issues? And then thirdly, think about the myeloma itself. How is it presented? Is it a slow biochemical relapse or indeed a much more of a “flamboyant” relapse, for want of a better expression? If we take that approach, it becomes a little easier for us to choose which is the best combination.

I gave a few examples. You can imagine if you have an older patient who's maybe on daratumumab, lenalidomide, and dexamethasone, if that patient was to maybe progress whilst receiving that therapy, it may be that you don't want to go straight away with another anti-CD38 molecule or indeed with another IMiD. It may be that you want to swap groups and use a proteasome inhibitor. You could potentially place that with one of the other monoclonal antibodies or indeed one of the targeted therapies, but it would be a matter of choosing drugs that the patient hasn't seen before to really maximize that clinical effect. Using that kind of framework of choosing which PI the patient might be resistant to or which IMiD the patient might be resistant to is very helpful moving forward.

When I'm talking about targeted drugs in this particular setting, then I'm really thinking about selinexor, which targets the XPO, or venetoclax, which seems to be particularly good for patients with an 11;14 translocation. In the monoclonal antibody setting, we've obviously got daratumumab and isatuximab, which targets CD38, but we also have elotuzumab and more recently belantamab mafodotin which targets BCMA. In the IMiD sector, we've got lenalidomide and pomalidomide, and in the proteasome section we've got bortezomib, carfilzomib, and ixazomib. 

Taking that structured approach of which drugs do I want to put in my combination, and then picking out which one's going to be best for my patient is going to be the right approach.

Source:

Davies, F. E. Updates In Early Relapse- Which Agents? Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY.