Management of Transplant-Ineligible Multiple Myeloma - Episode 5

Managing Adequate/Inadequate Treatment Response in MM

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Recommended next steps regarding treatment for patients with transplant-ineligible multiple myeloma based on prior responses to therapy.

Robert Orlowski, MD, PhD: Let’s go to the next polling question. If a patient achieves what you consider to be an adequate treatment response, what’s your next step? What are the options? Then we’ll discuss this as a panel. No. 1, continuing therapy as is. No. 2, changing the regimen to try to achieve an even better response—I guess this is if you’re not MRD [minimal residual response] negative. Or No.3, discontinuing therapy. Let’s see how the audience feels about this.

While we wait to see how people will vote, Larry, what would you do in this scenario? Let’s say you’ve given the patient induction. Whichever definition of response you’re looking for, let’s say you’ve reached that. What would you do? Here’s at least the initial polling, and it looks as if a lot of people would continue therapy as is. Larry?

Larry Anderson, MD, PhD: It depends on which therapy it is and how they’re tolerating it. After a certain number of cycles at the very least, we’d typically pare down the therapy but continue if they’re responding. The data we have are that the patients who stay on therapy the longest tend to have the longest remissions and best outcomes, so we’ll want to keep them on therapy. But if it’s a monoclonal, for example, those are easier to continue longer term, along with an IMiD [immunomodulatory drug]. If it’s a proteasome inhibitor, we might drop that out and keep them on a maintenance emit after several cycles but it depends on their chromosomes and if they’re having neuropathy and other adverse effects.

Robert Orlowski, MD, PhD: Let’s say for the sake of argument that the patient has an inadequate response. Caitlin, what would you do at that point? Let’s say you get a PR [partial response], but the patient is doing OK on therapy. It’s not a toxicity issue.

Caitlin Costello, MD: I talk to those patients about what their goals are. Are they interested in aggressive care? Are their goals of quality of life just the same? I can always do more. It doesn’t mean I should. Realistically, if someone is doing well on therapy but has not had an adequate response and is interested in pushing further, then it’s reasonable to change therapies. If a patient is on an IMiD proteasome inhibitor triplet, for example, that may be a good opportunity if they’ve had less than an adequate response to try something like a monoclonal antibody in combination with a second-generation emitter or a proteasome inhibitor. There’s no wrong answer. This is a discussion with your transplant-ineligible patient. If they’re willing to push harder, then I am if it’s reasonable and the toxicities are manageable. If it’s an adequate response and they’re willing to push them, then it’s reasonable to change.

Robert Orlowski, MD, PhD: What would you typically change to, Jeff? Let’s say you were in this situation, for the sake of argument that you did daratumumab, lenalidomide, and dexamethasone up front and you get a PR and then reach a plateau, but you’re not making any further ground. What would you do?

Jeff Matous, MD: That’s tough because that’s a great up-front regimen, and then you think about classes after that. Are you going to go to a proteasome inhibitor, maybe bortezomib or carfilzomib? Do you believe that if you switch out lenalidomide for pomalidomide you might get somewhere? Are you thinking clinical trial at that point? That’s a tough situation, but the other thing you can do is you can add. We have daratumumab-lenalidomide, and if your patient is tolerating daratumumab-lenalidomide pretty well, then maybe you add a proteasome inhibitor to the mix, make a triplet into a quad if you think they could handle it, and so forth. A lot of it depends on if you have someone you treated because they had a mild anemia, or they had a myeloma-defining event such as 2 focal bone lesions, a light-chain ratio. In these patients, I’m not going to push too hard, but if they had symptomatic bony disease, for example, I’m going to push them a little harder. Either making it a quad or swapping drugs out would be the major thing, but this is a group of patients for whom I’d be thinking about a clinical trial too, Bob.

Robert Orlowski, MD, PhD: Always a great option.

Transcript edited for clarity.