Advanced imaging tool improves detection of residual multiple myeloma disease

A targeted immunoPET scan detected active multiple myeloma that standard PET/CT scans and blood tests missed, a finding that could help doctors more accurately map disease, guide treatment decisions and confirm whether cancer remains after therapy. The phase 2 clinical trial was led by researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.

Multiple myeloma is a disease that can remain hidden in plain sight. This blood cancer grows in the bone marrow but spreads to many places in the body. Doctors can use advanced imaging and newer blood tests to look for disease, but these tests do not always tell the full story, which can affect everything from diagnosis to treatment decisions.

Now, Sylvester researchers have shown that a targeted imaging approach can detect active myeloma that standard tests miss. The study, published in Radiology, used immunoPET, a new type of labeled antibodies that find and attach directly to myeloma cells.

If we are going to cure multiple myeloma, we need two things. One, we need really effective medicines. Second, we need to be able to make sure there is no disease left behind after these treatments. We are developing new and better technology designed to see where the disease is and make sure we are not missing it."

C. Ola Landgren, M.D., Ph.D., chief of the Myeloma Division, director of Sylvester Myeloma Institute, and senior author of the study

More than 36,000 Americans are diagnosed with multiple myeloma each year. In the current standard of care setting, their disease progression is tracked using standard PET/CT scans, which rely on labeled glucose. The standard PET/CT scans are based on the idea that tumor cells consume larger amounts of glucose compared to surrounding normal cells. But for myeloma, this is not always true. In up to 40% of the cases, standard PET/CT scans miss residual disease because there is no abnormal glucose uptake.

"Myeloma cells frequently consume the same amount of glucose as the surrounding normal cells," Landgren said. "It's very well known among radiologists and myeloma experts that some patients who have myeloma in their bones may not light up on PET scans. The methods are simply not designed to reliably capture multiple myeloma."

To find newer and better ways to identify myeloma cells, the researchers developed a new compound to trace the cancer cells. Specifically, they labeled antibodies that are designed to recognize a myeloma-specific surface protein called CD38. Landgren and collaborators at Hoag Cancer Center first tested the idea in laboratory models before advancing it into early human studies and, now, a multicenter phase 2 clinical trial.

They enrolled 60 patients with multiple myeloma who underwent both a standard glucose-based PET/CT scan and their antibody-based scan, which they called immunoPET.

More than 10% of the patients showed disease signals only on the immunoPET scans. Follow-up biopsies confirmed that the immunoPET scan signals were active myeloma disease that the traditional PET/CT scans had missed.

For example, one patient had persistent back pain but normal blood markers and imaging. The immunoPET scan, however, revealed myeloma lesions in the spine. After the patient switched treatments, their pain resolved.

The technology also found myeloma cases that were far more extensive than expected. One patient had negative scans and blood tests, but the immunoPET scan found widespread disease. A follow-up biopsy confirmed it.

"Their standard tests showed no evidence of disease, but we found nearly 100 sites of myeloma throughout the body," Landgren said. "These are exactly the kinds of patients who benefit from better scans."

While in 17 patients (28%), immunoPET uncovered disease that standard PET/CT scans missed, the reverse was also true in 13 patients (22%). The two approaches detected a similar amount of disease in the remaining patients. No single imaging test identified every case of myeloma.

Rather than replacing existing tools, Landgren said, the goal is to add another layer of information. Together, blood tests, bone marrow biopsies and imaging each reveal important information.

"We show that you can successfully find much more disease," Landgren said. "It's a more sensitive and more precise technology, and we have very strong proof of principle that it works and that it's meaningful."

The current version of the scan still has limitations. For example, it takes a week for the antibody to travel through the body and attach to cancer cells, which makes administering the test more complicated. 

Landgren and his colleagues are already developing next-generation versions, using smaller antibody fragments that can reach tumors more quickly. This could enable a same-day test, making it more practical for routine use.