What are we learning about the optimal duration of bispecific antibody therapy?

Bispecific antibodies are an exciting new option for treating multiple myeloma. But one important question patients and doctors are still learning about is how long these therapies should be continued. In this video, we'll explore what current research is telling us about the optimal duration of bispecific antibody treatment, what factors may influence how long someone stays on therapy, and what this could mean for patients in the future.

What are we learning about the optimal duration of bispecific antibody therapy? There's a lot of uncertainty about how long we should be giving bispecific antibodies to patients. What's amazing about these drugs is that they're very, very effective in patients who respond, they tend to have complete responses. So very, very deep responses. And those responses occur quickly. And they occur in a, in a large portion of patients. And so even in relapsed refractory myeloma patients, the response rates are in the 60 to 70%.

So if you think about a typical patient, even in relapsed refractory myeloma, who gets a bispecific antibody in response that, you know, the response happened the first couple of months, where they keep getting the drug and the response can last for years. So they're getting the drug month after month after month for years. Right. And look, we a lot of myeloma therapies work that way. But with this therapy there are some downsides to giving it for a very long time. And one of them is risk of infection.

The other is that in order to prevent the infections that come with long term dosing over, at least the BCMA directed bispecific antibodies like teclistamab elranatamab, is patients have to be on IVIG which is an antibody replacement therapy. And so while the drug itself is just a shot in the belly and it's really easy on patients, the IVIG therapy is several hour infusion that they have to get every 1 to 2 months to support to, to basically give patients the antibodies they can't make on their own while they're on this medication.

We at Penn and actually HealthTree has been you know, helpful in advising us on this trial. We started a clinical trial for patients with relapsed refractory myeloma who are getting teclistamab, which was the first approved BCMA bispecific antibody and for whom the drug has been working very well for 6 to 9 months, just to stop and see what happens.

If we just stopped the medication and what prompted us to do this, in addition to the kind of the long term therapy that a lot of our patients were receiving, we just felt like maybe they don't need to be on it this long because they've been in a complete response for so long. We also had some occasional patients who had to stop the drug for a side effect. They got a bad infection or some other complication. inevitably, the patients who stopped the drug, they didn't relapse for, like, a long, long time. And some, some patients who stopped the drug years ago for a side effect, having relapsed.

And so we had these couple patients who had stopped it for incidental reasons, who looked like they were doing really well. So, like, why don't we try to do this more systematically and study whether we can stop this? And so we started this clinical trial, we call it the LimiTec study for limited duration teclistamab.

And it's taking patients who are getting teclistamab, with the FDA approved drug who have had a very good partial response or better, in reality, most of the patients are complete responders, 6 to 9 months. And then if they want to enroll in the trial, we stop it and we watch them very, very carefully. First time that the myeloma is growing, we restart teclistamab. And we're trying really to study whether or not it's safe to give patients a break and how they do.

And the goal is really to see in a preliminary fashion whether or not a short duration of therapy gives you similar results to what we would expect with continuous therapy. But we're optimistic. And I'll just say patients have had a really good experience on the trial. We have patients who have been, over two years off therapy. And it seems like the right thing to do for some patients.

I think we need more data with time to decide is this an approach that we should take for everybody, or are there certain patients that it makes more sense for? But the first step is just to study, and that's what we're trying to do in the LimiTec trial.

One of the greatest appeals of CAR-T cell therapy, for example, is that you give one time treatment. you deal with the toxicities usually for the first couple of months. And then patients can enjoy sometimes years long, remission without the need for ongoing therapy.

With bispecific, however, have been developed like any other drug in the relapsed refractory setting where you start a drug and you continue until the disease gets worse, which is, I think, a paradigm that we want to challenge. I think patients want to challenge when you have therapies that are so powerful and lead to so many patients achieving a remission early on, and the toxicities are considerable, particular in terms of, risk for infections, for example.

There is an interest in pursuing what's called, fixed duration therapy. Unfortunately, we don't have at the present time a good data to quote for fixed duration bispecific, because those, the data that support the approval of those therapies are patients from multiple lines of therapy, where people haven't taken the risk or taking the chance of designing a study for fixed duration.

But that would there's only one exception, which is a drug that is not yet approved called cevostamab. That by design is a one year therapy. And well, we have learned from that trial, even though different drug, different mechanism, a different target is that the majority of patients will sustain their remission for a very long time over a year. And when there is a recurrence of the disease, often the patients can respond to a challenge with the same drug.

I think is almost inevitable that as bispecific move into earlier lines of therapy that we're going to see more and more trials being designed with fixed duration. And hopefully over time, we're going to have some more guidance on how long patients should be staying on. What we know, however, with their existing drugs, with, the existing schedule is over time. And we learned that recently for talquetamab. But I believe that to be true with all of those, the drugs can be spaced out, without losing efficacy, which is another hard lesson that we were learning.

We can mitigate side effects and maintain efficacy by spacing the duration of therapy. And we are seeing that really evolving or new data, appearing even for the existing bispecific.

As bispecific antibody therapies continue to evolve, understanding how long to stay on treatment is an important and active area of research. While there isn't yet a one size fits all answer, ongoing studies are helping refine how these therapies are used to balance effectiveness, safety, and quality of life.

To learn more about the LimiTec trial that Doctor Ghaffar mentioned, watch the HealthTree conference news video on this trial.