With relapsed myeloma, when should you modify current therapy change dosage?

With relapsed myeloma, when should you modify current therapy as opposed to starting a new one?

Most patients who have disease that's becoming uncontrolled, and they're trying to see whether they can modify their current regimen. Usually, the modification of the current regimen is unlikely to be effective. There are two known things that can occur. One is that the addition of dexamethasone can provide some delay in the patient's myeloma and provide a period, potentially, of disease control, with the rest of the regimen staying the same.

And with Darzalex, patients can develop progressive disease, and then certain pairs will allow us to flip back from monthly Darzalex to weekly Darzalex, and that can sometimes get back disease control. Other changes, such as changing the dose of the IMiD or changing the dose of the proteasome inhibitor, are less likely to be effective.

So that's a great question, and it really does depend on the patient, and it also depends on the patient's disease.

Certainly in my practice, one of the guiding principles is trying to keep as many drugs available for the patient and many therapies available to the patient, as possible. Try to keep as many treatments in the toolbox, because for the vast majority of our myeloma patients, it's going to be a very long fight.

It's going to be years. And so you don't want to just waste all your drugs at the beginning or at the end and then not have anything.

So the key piece of the strategy that we use for treating myeloma patients is trying not to use drug A that will also cause resistance to drug B and drug C.

So instead of just becoming resistant to drug A, you've actually knocked out three drugs by using that. So a lot of how we design is that, for example, if a patient looks like they're beginning to relapse and we can add another drug to their current regimen,

to actually synergize with the current combination, we'll try that first. But a lot of it will actually depend on how quickly the person is relapsing.

So if it's a very slow relapse, it looks like the myeloma is getting slower, but they're really still facing a headwind. You know, they're really still struggling to grow. Then the addition of, you know, the replacement of one drug if you're taking 3 or 4 different drugs, replacing one drug with the next generation of drugs might be the way to go.

If somebody is just growing like gangbusters, right? They are just growing like crazy through all three drugs that they're currently on. There really tells us at that point, we really need to switch to something different. And what we want to do is switch to treatment that they are probably not going to be resistant to, right?

So if, for example, if a person is getting, what we call proteasome inhibitor like Velcade or Carfilzomib and they're just growing through that like crazy, it probably doesn't make any sense to give them another proteasome inhibitor in that same class, because that myeloma has already shown pretty good evidence that it's completely resistant to

that. So in that case, you would switch to something completely different, with the idea that, well, they seem to be resistant to everything that looks like this drug. So let's try something different. So it really does depend on the patient and how their myeloma is doing.