Is there a role for conventional chemotherapy in the treatment of relapsed and refractory myeloma?

Is there a role for conventional chemotherapy in the treatment of relapsed and refractory myeloma? What are some chemotherapy regimens to consider?

Yes there is you know you know, you never want to discount anything that you have in your toolbox. And patients, you know, do need conventional old fashioned chemotherapy, you know, especially if they have aggressive or rapidly growing disease or, you know, disease that is now circulating in the bloodstream or going to other places outside of the bone.

So extramedullary myeloma, and and then for our patients who have more aggressive kind of myeloma that we are trying to get to CAR-T cell therapies, many times the old fashioned chemotherapies are what control the disease long enough for our patients to get those kind of, you know, therapies. So think you have to use everything in the toolbox to help your patients.

You can't discount these treatments. You may displace them, you know, in terms of where they need to be in order of things. But I think, you know, we will be relying on all these tools together for best outcomes for our patients.

So when we talk about conventional chemotherapy regimens, they're typically with, you know, alkylator based treatments, drugs like bendamustine, melphalan and cyclophosphamide or regimens that, you know, including VDPace or DCEP, you know, can be utilized for myeloma patients.

the good news is that, you know, these infusions or, you know, alkylator therapies can work very rapidly, but they do have the old fashioned chemotherapy side effects, you know, of dropping the blood counts. patients, having, an increased infection risk, you know, alopecia or hair loss, can happen with some of those treatments as well.

But, you know, those side effects are transient, those treatments are not options we may pick for older myeloma patients. So you have to kind of, you know, balance patient factors with, you know, the disease factors to pick, you know, consider picking those treatments.

the question is how we use essentially conventional chemotherapy in treating relapse and refractory myeloma these days. And this gets back to regimens that we don't use too much anymore.

So we used these regimens often quite a bit before we had all the novel agents that are available currently. And so basically what all this refers to and what we think about with conventional chemotherapy are these are old school chemotherapy medications that, you know, most medications for myeloma these days don't have kind of what I

think of as the usual chemotherapy side effects, hair falls out, severe nausea, hospitalization due to severely low blood counts, diarrhea, mouth sores.

That's all old school chemotherapy that we don't see too much in myeloma anymore.

Conventional chemotherapy is those agents and still has those side effects. And so the things to keep in mind about conventional chemotherapy are that we just don't do it much anymore

because we have so many other options which are often more effective. They're smarter in the sense that they're much more targeted.

And the side effect profile is usually a whole lot more manageable.

so we don't do those much, but we still do them sometimes. And I would say that we most often do regimens like that when a person's myeloma is likely or refractory or resistant to a lot of the novel agents, meaning they've been through, let's say daratumumab, and Velcade and REVLIMID and Pomalidomide and medications like that.

Their myeloma seen those tricks before and is unlikely to respond to those and we’ll often do conventional chemotherapy as a bridge to something better. So it could be as a bridge, meaning we're trying to get the person on a clinical study or there's another medication that's likely to be approved in a couple of months. And we're trying to keep their myeloma under control for long enough to get them to that.

Or for example, we're trying to get them to CAR-T and we've collected cells for CAR-T, Those cells are being processed and we need to keep a lid on the myeloma for long enough that they can then get that and that CAR-T infusion that will hopefully provide more durable myeloma control.

So suffice it to say that we don't love using conventional chemotherapy anymore because the one thing that's certain about conventional chemotherapy is that it's more toxic than most other things we do, but we do it when push comes to shove, if we need to keep myeloma under control again as a bridge to some better option.

And then just in terms of what what regimens are available, there are a number that are out there. They've never really been looked at head to head.

A couple of them are DCEP There's another one VDT Pace, there's another one VAC, other ones like that, you can even use kind of intermediate dose melphalan where malphalan is the drug that we use for transplant.

And so we can use that as a lower at a lower dose where you don't need the transplant, but it still has a lot of the same side effects.

Again, none of them have been looked at head to head, but there are reasonable options when we're looking for a conventional chemotherapy as a bridge. But we don't we don't like doing those those regimens much anymore.

We do them if we have to, though.