ASH 2025 Myeloma Update: Bispecific Antibodies & 3-Year Remission Data 

Dr. Joseph Mikhael:

This is one of the most viewed and shared images from the American Society of Hematology meeting this year in multiple myeloma. You may wonder, what does that number mean? What do those lines mean? Well, stay with me and I'll share with you what this means and how it will likely change the way we treat multiple myeloma.

Hi everyone. Dr. Joseph Mikhael here, chief medical officer of the International Myeloma Foundation, where we are committed to the quality of life of patients as we seek prevention and a cure.

In the earlier video, you saw me highlight the top five abstracts presented at ASH or the American Society of Hematology in CAR T-cell therapy. Well, now we're going to look at another five abstracts, but in the realm of bispecific antibodies. To quickly review, bispecific antibodies are those drugs that have two arms. One arm grabs onto the myeloma, another to a T-cell that is in a patient's body, those T-cells are like soldier cells, and engages that T-cell to destroy their multiple myeloma.

The first abstract I want to talk to you about is the one that has that famous image. It was the combination of teclistamab, a bispecific antibody we already use and daratumumab a monoclonal antibody we already use, but now combined together in patients that had one to three prior lines of therapy. You may remember in my overview that I demonstrated at three years over 80% of these patients were still in remission. As we think deeply about this abstract, what does it mean for patients? I think this is particularly important for several reasons.

First of all, we can combine these two antibodies together and deliver them to a patient at the same time. We've also noticed that when we give the teclistamab, we're giving it less frequently than we've historically given it, and so we've seen fewer side effects. Perhaps most importantly, we saw a response rate and a duration of response that we've never seen before in early relapse. Again, at three years over 80% of patients still in remission.

Now, there was a bit of a challenge in this study that there were patients who experienced some very serious infections, and there were patients unfortunately who died of those infections. But the protocol was changed and more careful attention was paid to infections. So as we go forward, we know how to use this combination more effectively. Almost definitely will we see this combination in the clinic very soon, and I'm excited to use it for my patients.

The second abstract we talked about was the same combination teclistamab and daratumumab, but now used in front-line therapy in patients who were typically not going to an autologous stem cell transplant. And even though the numbers were small, we saw that literally every patient responded to this and stayed in response to this in their first year.

Why is this important? We know that it's difficult to treat multiple myeloma in the first line. We know that some of the drugs we use come with different side effects that can make it very difficult for patients to stay on those therapies. It was remarkable in this study how deep and durable those responses were and how well tolerated this combination was. I think we will see a change in the way we treat frontline therapy of multiple myeloma as we bring bispecifics into that frontline.

The third abstract we discussed in our overview was a unique way of incorporating a bispecific antibody into the overall treatment of multiple myeloma. We've learned, and we've been working very hard at the IMF to understand the importance of MRD, or minimal residual disease, negativity when we get someone down to a point where we can't even measure their disease, and you may remember this was the study where patients were given their initial treatment and if they didn't quite get to MRD negativity, they were given a short course of a bispecific antibody called linvoseltamab, and all of those patients that were MRD positive were converted to MRD negativity.

I think this is really important because as we seek to overcome myeloma, we've learned that we have to come at myeloma in different ways and when we can use a different tool to attack myeloma, even if there's just a tiny bit of myeloma left, we believe it can translate into a longer remission for patients. So I think this strategy of incorporating bispecifics to achieve MRD negativity is going to be one of the ways we will attack myeloma in the future.

Let me pause here for a moment. You may be listening to all of this and wonder, "How can I keep up with all this great research?" Well, we've created a way to deliver that research personally to you in real time. If you subscribe at subscribe.myeloma.org, you will receive our newsletter that brings up-to-date information in clinical trials, in new publications, in new approvals of drugs, so that you can be the most up-to-date that you can in multiple myeloma. At the IMF, we believe that information is power and we want to empower you to understand your disease better, to be able to ask the right questions of your team, that together we can improve the lives of patients with multiple myeloma and indeed find the cure.

The fourth abstract was also an interesting incorporation of bispecific antibodies, and in this time it was after CAR T-cell therapy. We know and we've talked about how CAR T-cell therapy has really changed the way we treat multiple myeloma, but can we make it even more effective? We know that there are some patients that after CAR T, not long after their disease starts to grow again, because those cars run out of gas. They don't last that long in the system. But maybe if we gave patients a short course of a bispecific antibody after their CAR T-cell therapy, and at that a bispecific antibody that targets a different part of the cell that was not used in CAR T-cell therapy, in this case cevostamab targeting FcRH5, maybe the outcomes can be better. And it was remarkable to see that 100% of those patients stayed in MRD negativity. So I think we will learn more from this study and we will be incorporating more of this kind of approach in other studies as we seek to better the use of CAR T-cell therapy and make it last even longer.

And lastly, our fifth abstract was a very potent combination of teclistamab and talquetamab, two drugs that we use now separately, but combining them together in perhaps the most aggressive form of multiple myeloma, what we call extra medullary disease, or when the myeloma grows outside of the bone marrow. Sadly, we know that extra medullary disease is very difficult to treat. Many of our patients just don't respond to the treatments we give them. And if they do, it's for a very short period of time. And here, this combination showed that not only did 80% of patients respond, they responded for a longer period of time than we've ever seen before. So as we think of the spectrum of risk of myeloma, this is at the highest end of that risk. And those patients didn't have a lot of choice before and options before, and I believe this will be an excellent option for them in the future.

So there you have it. Five abstracts, novel ways of using the bispecific antibodies we have and bringing in new bispecific antibodies in the future, and even putting them into unique combinations so that we can improve the depth and the duration of response, and of course improve the quality of life of our patients with multiple myeloma.

Well, thanks so much for joining me today, and please don't forget to subscribe to our YouTube channel, you can do so at subscribe.myeloma.org, so you will be in the know and get our newsletters to know when the latest research is coming out, when the next video is out, so you can stay up to date in all things multiple myeloma.