89Zr-DFO-daratumumab Has Potential Imaging Benefits in Non-FDG–Avid Multiple Myeloma

89Zr-DFO-daratumumab shows activity in identifying and localizing multiple myeloma, even in FDG-non-avid cases, per new phase 2 data.

The radiolabeled imaging agent 89Zr-DFO-daratumumab demonstrated the ability to identify and localize multiple myeloma through PET/CT, including in patients for whom their disease is not fludeoxyglucose (FDG)-avid, according to results of a phase 2 study (NCT04814615) presented at the 2025 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Meeting.1

Of the 52 of the planned 60 patients that have been accrued to the trial, 29% had disease seen on the 89Zr-DFO-daratumumab PET that was not visualized on FDG PET, and 21% had disease visualized on FDG PET but not with 89Zr-DFO-daratumumab PET. There was an equal detection of lesions (50%) across both imaging tools.

“The current phase 2 trial demonstrates approximately 30% of patients have disease better visualized on 89Zr-DFO-daratumumab PET/CT than on FDG PET/CT,” lead study author Gary Ulaner, MD, PhD, FSNMMI, FACNM, the James and Pamela Muzzy Endowed Chair of Molecular Imaging & Therapy Hoag Family Cancer Institute, and professor of radiology and translational genomics at the University of Southern California, said in an oral presentation of the data. “My overall conclusion is that in patients with a non-FDG–avid [multiple] myeloma, 89Zr-DFO-daratumumab PET/CT could be useful for determining disease extent and location and for providing an imaging study for evaluation of treatment response.”

FDG/PET is negative in 20% to 30% of patients with established multiple myeloma lytic bone disease, with high false positivity rates due to inflammatory and degenerative causes, Ulaner noted, adding that invasive bone marrow biopsies are inherently limited by sampling error.

The CD38-targeted monoclonal antibody daratumumab (Darzalex) can be linked with zirconium 89, with preclinical data showcasing CD38-positive multiple myeloma in mouse models.2 In a first-in-human trial (NCT03665155), disease pathology was initially assessed to confirm CD38-positive multiple myeloma before undergoing 89Zr-DFO-daratumumab on day 1 of treatment. The coprimary end points were safety, optimal imaging parameters, and the ability to image known CD38-positive metastases. Results showed that the imaging agent continued to be visible at 7 days following initial treatment with 89Zr-DFO-daratumumab.2

In the phase 2 trial conducted at Hoag Family Cancer Institute and the University of Miami, a planned 60 patients with CD38-positive multiple myeloma were to undergo a pretreatment evaluation of standard labs, imaging, and blind bone marrow biopsy, followed by baseline 89Zr-DFO-daratumumab PET/CT and a possible biopsy of 89Zr-DFO-daratumumab–avid lesion. Patients will then receive standard-of-care therapy, defined by their medical oncologist, for up to 12 four-week cycles. Standard labs, imaging, and blind bone marrow biopsies are given until complete response is suspected, or 12 cycles are completed.

Posttreatment evaluations included standard labels, imaging, and blinded bone marrow biopsy before going through follow-up research of 89Zr-DFO-daratumumab PET/CT and another possible biopsy of 89Zr-DFO-daratumumab, before moving into the data analysis phase. At the 2025 SNMMI meeting, Ulaner discussed the results of the pretreatment evaluation.

“Not to say that this is a panacea, because about 20% of patients have disease on the FDG PET, which is not seen with daratumumab.” Ulaner said. “[It’s] not the wonder that we were hoping for, but still extremely valuable, particularly in the patients where the FDG PET fails to demonstrate disease.”

Ulaner cited a case example of a 76-year-old man with biochemically relapsed multiple myeloma for which no foci were detected via FDG PET, but more than 100 osseous foci were identified via 89Zr-DFO-daratumumab along with a biopsy-proven lesion in the left femur. The patient then initiated treatment with daratumumab, lenalidomide (Revlimid), and dexamethasone.

Another highlighted case, however, was in a 29-year-old woman with newly diagnosed multiple myeloma with no foci visualized with FDG PET, but osseous foci were found on 89Zr-DFO-daratumumab and biopsy-proven myeloma in the left scapula.

“No test is perfect, and here we were already begun to able to see our false, false positive findings,” Ulaner said. “This patient had bilateral adrenal uptake, which turned out to be bilateral adrenal adenomas.”

Editor’s Note: Ulaner cited research grants with NIH R01, Department of Defense, Komen for the Cure Foundation, and Leukemia & Lymphoma Society; and consultant, advisory board, and/or lecturer roles with GE Healthcare/Zionexa, Genentech, ImaginAB, Lantheus, Novartis, Nuclidium, Puma Biotechnology, Sanofi, and Siemens.

References

1. Ulaner GA. A phase 2 trial of 89Zr-DFO-daratumumab for CD38-targeted immunoPET of multiple myeloma. Presented at: 2025 Society of Nuclear Medicine and Molecular Imaging Meeting; June 21-24, 2025; New Orleans, LA.
2. Ulaner GA, Sobol NB, O’Donoghue JA, et al. CD38-targeted immuno-PETof Multiple Myeloma: From Xenograft Models to First-in-Human Imaging. Radiology. 2020;295(3):606-615. doi:10.1148/radiol.2020192621