Bispecific Therapies in Myeloma: Preferences & Priorities | Thomas LeBlanc, MD

I'm Tom LeBlanc from the Duke Cancer Institute in Durham, North Carolina.

And I'm excited to talk with you all about our abstract on patients with relapsed or refractory multiple myeloma, around preferences and values for bispecific antibody therapy.

The back story is that patients with multiple myeloma have various new targeted treatment options available, but they all have trade-offs.

This new category of bispecific therapies activates the immune system against the cancer cells, in this case, the plasma cells that are the cancerous cells of multiple myeloma.

But by activating the immune system, you can also cause a little bit too much inflammation or sort of too much chaos that can make the patient sick while you're trying to help them feel better and treat the disease.

There are now at least three different FDA approved bispecific therapies. The numbers keep growing in multiple myeloma.

So what we did is we found five patients with a history of multiple myeloma from six different countries, including the U.S. and five European countries.

We did kind of open-ended, semi-structured interviews with them to better understand what they feel is most important about a treatment that they would get in the relapsed or refractory myeloma setting, but with particular anchors around the types of things we know are issues with these bispecific therapies.

For example, ICANS, or what we call sometimes neurotoxicity, is a kind of confusion-related syndrome from the immune-related activation. It's probably something that we usually manage pretty well with treatment, but it's also a scary thing when it happens.

We wondered how much that might be driving patients’ preferences about these new treatments.

We also tied the questions we asked folks to the kind of plausible, expected toxicities that we would see with the different available therapies in this space.

For example, elranatamab, teclistamab, and talquetamab, among others. This made it a bit more realistic that we were asking people about the kinds of trade-offs that they really would be facing if they're deciding between these different therapies.

What we found in interviewing these 30 patients from around the world is in some part not very surprising, but then also there are opportunities for further study and some interesting areas that we didn't necessarily expect but want to focus on in future research.

For example, the not-surprising piece that was most common that we heard from patients is that efficacy really is the main driver of their interest in a particular treatment.

The part that also seems to be a big driver for many patients, though, is the option for time off treatment. So if you could get a treatment that's time-limited and stay off thereafter for a while, that's particularly important.

A really close second to efficacy were concerns about not necessarily specific toxicities, but much more holistic thoughts about function and quality of life, which makes sense.

When it comes down to brass tacks, are people worried about some specific side effect, or are they more worried about can they do the things they want to do? Can they function? Can they do their daily activities?

Most of what we heard was about the latter.

But then there was specific concern about this neurotoxicity or ICANS issue, where patients are particularly worried about that kind of frightening, confusional state that can happen as a short-term side effect of these therapies. This is something we need to drill down on in future research.

The reason why this is important is that we're using the results of this interview study to inform the creation of what's called a discrete choice experiment, or a DCE.

This is where we take these more subjective insights from an interview and then turn them into a more quantitative study, where we actually ask patients to rate how much they would weigh and value these things.

If you had to choose, how many points would you put on efficacy, how many points on toxicity, avoidance of certain toxicities, etc., to come down to a more quantitative estimate of what really drives people's decision of one therapy over another.

As we start to do more Car-T cell therapy in myeloma, which is another type of immune cell effector therapy, we need to better understand how people prioritize things like time off therapy versus continued time on therapy, but maybe with less risk of severe toxicities.

So that'll probably be the next phase of some of this work.