Maintenance Therapy for Multiple Myeloma

Transcript: Paul Richardson, MD: A final point about the MRD [minimal residual disease] points that we’ve already I think discussed comprehensively, Ajai, is to ask you about how you treat an MRD-positive patient who cannot undergo transplant. What do you do in your practice?

Ajai Chari, MD: I think it goes back to the time point assessment. Whether it’s transplant or not, obviously I don’t think it would be prudent to discontinue therapy, but you may see intensification of that response with continued treatment. I think I would probably either consider tweaking the regimen and so for example, maybe switching PIs [proteasome inhibitors] to a more potent one or maintaining the DEX [dexamethasone] if it had been omitted, something like those kind of things. I think more important than depth of response is duration of response. As long as you’re not relapsing clinically, and I think that’s another thing we didn’t discuss earlier, the functional risk of the patient is increasingly important.

Paul Richardson, MD: In that context, the duration of maintenance, we’re coming to that in a minute. Sorry, Amrita.

Amrita Y. Krishnan, MD: I was going to say, do we really have any data that intervening earlier is going to have any impact?

Ajai Chari, MD: I think the summary statement for MRD is it’s a prognostic test but not a predictive test.

Paul Richardson, MD: That’s well said. And continuity of assessment is critical. I want to now, Nina, ask you to help us think about optimal approaches to maintenance therapy and obviously recognizing that there are some studies that are going to try and look at de-escalation, but we obviously approach that with great caution. Tell me your thoughts. How do you think about maintenance strategies for your patients?

Nina Shah, MD: I think the original data that we had looked at European versus American, etcetera, basically showed us that longer maintenance is better. There have been older trials that have shown that more maintenance, meaning dose intensity, is better. It’s hard because the real-world situation is it’s difficult to tolerate, especially maybe after you’ve had a transplant.

In that situation, there are ways to think about is there a way to de-escalate and there are trials being planned, for example, the SWOG based on an MRD analysis, if you’re negative potentially you could come off. There are ways to look at MRD, maybe to predict if you should get more maintenance. So, in the AURIGA trial, if you’re MRD-positive and in CR [complete response] or VGPR [very good partial response] after transplant, you’ll be eligible to be randomized to DARA/LEN [daratumumab, lenalidomide] versus LEN [lenalidomide] for 3 years. That has an MRD-negative end point at 12 months.

Now we’re going to be able to use MRD and the fact that we have a little flexibility with drugs with maintenance, actually to try to make decisions and look at that, similar to what Luciano Costa, MD, PhD, is doing in the upfront setting, but now with a little bit longer-term treatment paradigm and also maybe a little bit more knowledge. But again, right now, we should not be making decisions based on it. I know that anecdotally, a lot of people say, for a person who’s been on lenalidomide for 3 years, they’re not tolerating it, I will do a bone marrow biopsy. If they’re MRD-negative, we’ll have a discussion and say, OK, you can stop, I’m OK with that, and that’s OK. Every patient is an individual and not a data point.

Paul G. Richardson, MD: Well said.

Amrita Y. Krishnan, MD: Can I make a comment?

Paul G. Richardson, MD: Yes.

Amrita Y. Krishnan, MD: Even though Sagar is not Mr. OS [overall survival], maybe I can convince him that the end point is OS. The end point of the SWOG trial is overall survival because we all agree MRD is clearly correlated with PFS [progression-free survival]. But really is your intervention affecting OS at the end of the day.

Paul G. Richardson, MD: This particular trial, which is obviously lenalidomide versus lenalidomide and daratumumab with this early stop for selected patients, will really help sort that out.

Sagar Lonial, MD, FACP: I think that most of the trials that went into the meta-analysis that showed PFS and OS benefit for MRD as a prognostic marker were using European trials with limited-duration maintenance.

Paul Richardson, MD: Right, exactly. That’s a great point, actually.

Sagar Lonial, MD, FACP: When we give continuous maintenance, it changes the whole outlook. The example I’ll give is, I’ve got lots of people who are not in CR who are doing well on lenalidomide maintenance. I’ve got lots of people who are MRD-positive who are doing well on lenalidomide maintenance.

Ajai Chari, MD: Of course, the other point is drug access. It’s not just duration. Because all it takes in this study would be an imbalance in access to BCMA [B-cell maturation antigen] therapies, and there goes your OS.

Paul Richardson, MD: Your OS signal, yes. Sagar, I completely agree with you. The impact of maintenance, and we’re clearly getting a clue from our studies to show that.

Transcript Edited for Clarity