Finding Hidden Myeloma Using IMMunoPET Imaging Technology | Ola Landgren, MD, PhD

I'm Ola Landgren.

I'm professor of medicine, and I'm chief of the myeloma program at the University of Miami in Miami, Florida.

I'm here at ASH 2025, in Orlando, Florida.

So lots of new information coming out in different ways. New treatments, both for patients with smoldering myeloma and newly diagnosed and in relapsed myeloma. There's also a lot of biology information. A lot of the new assays that are being developed for the disease is really an exciting time.

One of our presentations focuses on IMMunoPET, and what we have done is that we have asked ourselves, how can we improve imaging in multiple myeloma?

And if you think about for a while how imaging has evolved in parallel with all the treatments, it has actually been a lot of development. Several years ago, we used standard x-ray that is very inferior. Over time, we started using PET scans, PET CT machines, and in Europe and elsewhere they use CT alone. And also MRI machines have been used. And we have also used PET MRI. So integration of all these different approaches.

But the problem that has continued to be present in the clinical setting is that not every patient is actually captured with these technologies. And if you use the PET tracer in the setting of MRI or in the CT machine, you will miss approximately 30% of the cases because the disease is very slow. And the FDG PET CT, which is the standard of care, uses glucose. And if the disease is relatively slow, which it is in 30% of patients, there is not enough glucose consumption to light up. So you will not see anything. It's going to be negative. You can look and see for CT changes, but many times that can also be missed. Why did right radiologists if they don't look for PETs abnormality. And that can happen. We have seen that for years.

So that led us to believe that we could label antibodies. And we worked on this. And I worked on this for many years when I used to lead a program at Sloan-Kettering, and I took it with me to the University of Miami, and we worked together also with Hoag Cancer Center, with my long-term colleague and friend, Gary Ulaner.

So Gary and I, we wrote an R01 grant, and we got funding to label darzalex with zirconium-89. And if you first label it with DFO key later and then label that with zirconium-89. So this is an immunologic tracer. So it binds to the disease. It's not glucose.

The same way we treat the disease with targeted therapy, this is targeted imaging. And that has not been done in the phase two study for myeloma previously.

We did work in mice when I was at Sloan-Kettering. And we also did a phase one study with step-up dosing, figuring out how to do it. But now we have done the phase two study and that's what we are presenting. The final results. This study here at ASH 2025.

And what we show is that for those cases that are negative with the standard FDG PET CT, which is a standard of care, we see uptake with this targeted antibody labeled IMMunoPETs, so we can pick up the disease in those cases also.

And what we also see with this study is that not only do we pick up those areas that are positive by a FDG PET CT cases that are positive, we can also see many more sites. And there are some dramatic cases where the FDG PET CT has been completely negative, and we have seen up to 100 sites of residual disease. These are very small sites of disease and these are biopsied in many of the cases. There is evidence of disease.

So that has led us to wonder, is this why we have not in the past been able to cure patients because there is hidden disease that we miss with standard technology.

So I think going forward, we should really think about developing more sophisticated tools. And we are working for next generation imaging and we use full antibodies. We are looking into using nanobodies that are parts of antibodies that have certain benefits for feasibility, is much quicker to do, and also using small molecules.

But overall the field of imaging has been sort of resting and not been pushed forward. And we are trying to do our best to push that forward, and we need other groups to help and do that as well.

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