Choosing a Treatment Strategy for Patients With Early Relapsed Multiple Myeloma

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, New York, Faith E. Davies, MD, Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, New York, discussed strategies for choosing between existing treatment options for patients with early relapsed multiple myeloma. 

Transcript:

Hi, I am Faith Davies and I'm a professor at NYU Grossman School of Medicine in New York, and I am here at the Lymphoma, Leukemia and Myeloma Congress in 2023. I have been talking in one of the myeloma sessions about early relapse of patients, so those patients between first and third relapse. And given the plethora of treatments we have available, which ones should we choose and how do we go about choosing those most appropriate treatments? 

I've been trying to think about it in a very logical way. So as with anything, it's making sure you have all the information at hand, really ensuring how the patient got on with their previous therapy, what their response was and what their toxicity is. And then thinking, moving forward, how their actual disease has relapsed. Has it been quick? Has it been slow? But also, have their cytogenetic changes altered at all?

And then from a pure patient perspective, what's their renal function like? What's their performance status like? And then what are their choices? How do they feel about their relapse therapy? Taking all of those into account, I then sit and do a bit of math, I guess. We know that patients respond better to either a doublet or a triplet. We know that ideally, we want to carry on whatever therapy we're going to give until either toxicity or disease relapse. And so, we know we want to manage patient's toxicities as they go through their treatment. We also know that as patients have responded, once they're in a good response, we can think about backing down a little bit on our therapies.

If we think about it, we've got proteasome inhibitors [immunomodulatory drugs] (IMiDs), monoclonal antibodies, and then targeted therapies [;] so, things like selinexor or venetoclax. Taking the logic, we want to do some form of combination, be it 2 or 3 of those drugs. I think one of the good examples would be a patient who maybe relapses off frontline therapy, maybe something like [daratumumab plus lenalidomide and dexamethasone] (Dara-Rd.) And in that situation, we're unlikely, because the patient has relapsed off a monoclonal antibody against CD38 and off IMiD, in an ideal world, we want to try and change class to make sure that we have good response rates.

In that situation, we may be thinking about having a proteasome inhibitor, maybe thinking about combining it with one of our targeted therapies, or indeed a monoclonal antibody that maybe hits a different target. We can also use pomalidomide, because we know that there are patients who will respond to [it] even if they failed lenalidomide. Taking that kind of logical approach and working out which different drug classes we want in our combination is important.

We've also spent a little bit of time talking about some of the new data. There's some great new overall survival data for isatuximab in combination with carfilzomib [and] LEN-DEX, really showing that as well as having a good progression-free survival there's an improvement in overall survival of at least a year. 

We spent a little bit of time discussing the new CANOVA data, which was a phase 3 clinical trial comparing venetoclax against pomalidomide in patients with an 11;14 [translocation]. And essentially, that trial didn't quite reach its statistical significance, but it did show that patients with an 11;14 have a longer progression-free survival and better responses to the venetoclax compared to the pomalidomide.

In closing, the thing that I'm most pleased about is that I'm doing this talk this year, because some of the data that my colleagues have been talking about has shown that the CAR-T cells seem to be incredibly effective in that first to third relapse setting. 

We know that there's going to be data on bispecifics coming up in the next year or so, which one assumes will also show efficacy in that setting. And so, we're probably going from about 14 different drug combinations we can currently use in that 1 to 3 setting to many more. I think it's a great thing for patients, and I'm not sure we can make a wrong decision. It's just trying to make sure we make the right decision for each individual patient.

Source:

Davies F. The Early Relapsing Patient. When to Rechallenge or Change Class? Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY