EHA 2024 | Reducing the financial and time toxicities associated with multiple myeloma treatment

This is a follow-up to some of our work at the IMS meeting and ASH last year. So just to reorient the audience, financial toxicity is a very real phenomenon, right? It’s the actual detriment to patients’ well-being that comes from the costs of living with cancer, receiving cancer treatment, etc. Time toxicity is what I would define as the detriment to patients’ quality of life from what I would say is unnecessary time on healthcare interactions. Obviously, when patients, you know…newly diagnosed patients, for example, have a very high threshold, and if you talk to them, yes, they’re willing to come in every single day if it will put them into remission. Once they’re in remission, then you start really wondering, is that extra clinic visit, that extra blood work, etc., actually making a difference for their long-term outcomes or not?

And so basically, previously, we had shown that about a quarter of patients with myeloma, regardless of what stage of the disease they were in or what phase, I should say, induction versus maintenance versus remission, reported financial toxicity. Very consistent, which is surprising to me because I would have thought that maybe financial toxicity would be worse for patients receiving active treatment and not those who were in remission. But it doesn’t change.

Time toxicity certainly was higher for the patients who were on active treatment, but again, many of them are okay with that, but a third of patients in remission still reported time toxicity.

And so, where are we going with this? Kind of working on things on two fronts: on the financial toxicity front, my co-author here at Fred Hutchinson Cancer Center, Chris Su, is working now on a kind of related concept called financial fragility, which is not just how high out-of-pocket costs are, because obviously, for some patients, an out-of-pocket cost of 100 USD per month is nothing, for others, it’s a lot. But looking at the repercussions of that, what percent of patients actually have to have their credit score get lowered, go into medical bankruptcy, take on debt, miss other payments, have to stop eating food, or dip into the retirement savings. Things that we know very little about as physicians. So there I think we’re still in a journey of learning. He actually presented a poster about this at the ASCO meeting earlier this year, using a large Washington state in the US database to leverage and find out who’s experiencing financial fragility. Unsurprisingly, we found that patients with financial fragility were less likely to receive four drug regimens for as long, and less likely to receive transplant in myeloma.

So now that we can show that, we can find the data and identify these vulnerable patients. Next step is how do we fix it? So stay tuned on that front.

In terms of time toxicity, I think the question, and we’re kind of alluding to this with the carfilzomib project, is perhaps instead of dosing drugs as frequently, maybe we can de-escalate them and get the same results. Both of the posters I’m presenting at EHA, the teclistamab one, again, showing you don’t need to dose it once per week, you can go to once every other week or every once a month, and the carfilzomib saying why dose it twice a week if you can dose it once a week, are helpful. 

Retrospective data have their limitations, I’ll be the first to acknowledge that, and so we’re looking into this prospectively. And so actually, we’ll be presenting a trial in progress at ASH, but we actually have funding now, thanks to Sanofi, for a study of IsaKRd in the front line setting, similar to ISKIA, but the dexamethasone is dropped after a couple cycles. As all of you know, that’s a topic of passion near and dear to me. But for patients who achieve a level of remission, for example, there’s a simple step- the day eight carfilzomib dose is dropped. We’re already doing once weekly to begin with, but you can imagine that with these measurements in myeloma, typically bortezomib is dosed days one, eight and 15 and skip 22, for example, and carfilzomib the same one, eight, 15, skip 22. If you pair with a CD38, you end up having these weird days where sometimes patients get two drugs, sometimes they get one, sometimes two, sometimes one. Once they’ve achieved a response, what’s the point of having that one drug day when they think they’re going to be just fine? So we’re actually testing that prospectively because I think it’s one thing for me to say that, oh, we’re overtreating our patients in hindsight where we’re missing some patients, data are missing, real-world data has limitations.

We’re looking at this prospectively because I think if we can show in a prospective manner that, you know, decreased time in clinic achieves equally optimal outcomes, I think that will be a big step forward for time toxicity and, in all honesty, for a lot of these patients, time and financial toxicity are closely intertwined, right? The reason they can’t maintain their livelihood, as for example, a contract employer or driver is because they have to come into clinic so often, you know, they have to take more time off from work. And so I think if we can tackle one, we may be able to tackle the other one as well.