ASH 2025 | The iMMunoPET trial: 89Zr-DFO-daratumumab for CD38-targeted imaging of multiple myeloma

The Immunopet study is work that we have developed ourselves all the way from preclinical work in mice into a phase one study that we have already published. And here at ASH of 2025, we show the final results from the Immunopet phase two study. This is an R01 funded study. I hold an R01 grant together with my long-term friend and colleague, Gary Ulaner, at the Hoag University in California. So what we have done is that we have taken this antibody, we have linked DFO to CD38 antibody, and then we have labeled that with zirconium-89. So instead of using glucose, which is a standard approach for standard PET-CT, so-called FDG PET-CT, you inject glucose and you take pictures and see where there is more glucose being consumed or not, which would be a measure of potentially diseased cells, because diseased cells usually eat more glucose than normal cells. This approach is very different. So here is no glucose involved. It’s an antibody. So it’s actually targeted imaging. So the whole reason for this is that in myeloma, the cells usually don’t eat as much glucose as you could see in other diseases. So the classical examples would be, say, Burkitt lymphoma or other types of very proliferative diseases. You can see very high glucose uptake, and the PET-CT is very, very useful. In many lymphomas in general, the PET-CT, the standard FDG, works really well. But myeloma is the opposite. And you can actually see that probably 30% of all the patients with myeloma, they’re completely negative for standard PET-CT. There’s no increased SUV. So recognizing this for many years, that really stimulated me to think about how we could develop it. And I worked initially with Jason Lewis at Sloan Kettering, and we did all the work together in the mice, and then we took it into the patients. So here at ASH, we show that in a cohort of 60 patients, that is the entire study for the phase two component of the study, that we can see evidence of disease in all those patients where the regular FDG PET CT is negative. I think that’s a very important step forward. Also, what we see is that in patients that are FDG both positive and negative, you can see more sites of disease because it’s a more sensitive approach. It’s a targeted imaging approach. So on our presentation here at ASH, we give a couple of examples of some extreme situations. We have one case where the regular FDG PET CT is completely negative, while the Immunopet shows about 100 sites of active disease. So you could imagine that perhaps that’s why the disease doesn’t always go away. That’s why there are relapses, because we really don’t have the tools to find the disease. So I’m very excited about this. This is now finalized. We have just written up and submitted the final manuscript, so we hope to publish that very soon. And we’re also thinking about what would be the next step going forward. There’s really nothing else going on at this time in myeloma on a clinical note. People have tried to do this in mice. It’s very complicated. So when you inject antibodies, they take about a week to penetrate all the tissues in the body. So if you inject a labeled antibody at a very low dose, it still takes about a week. So the patient has to get that injection and then come back a week later and do the pictures. So from a patient perspective, it’s not really very practical. So you could do other things. You could cut off the heavy part of the antibody and do nanobodies, which are just like fragments of the antibodies. And they can penetrate the tissues in hours or a very, very short period of time. So I think that would be an improvement. We had to start somewhere, and we wanted to build proof of principle, so that’s what we have done. And also we are looking into using even small molecules. You can actually have small molecules that can go after targets of your interest. And you could even think about having multiple different targets, just like, let’s say, a flow cytometry machine. You can look to see if the cells express certain epitopes or you could do sequencing, you can look for mutations, you can do the same with imaging, you could image and see if your targets are there, so I think this is the beginning of a potential big area of development.

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