Phase 2 Trial of ⁸⁹Zr-Deferoxamine-Daratumumab for CD38-targeted Immuno-PET/CT Detection of Multiple Myeloma.

Abstract

Background Multiple myeloma (MM) imaging is currently suboptimal, which may limit patient care. Zirconium 89 (⁸⁹Zr) deferoxamine (DFO)-daratumumab is a novel CD38-targeted immuno-PET tracer. Purpose To compare ⁸⁹Zr-DFO-daratumumab PET/CT against standard-of-care fluorine 18 (¹⁸F) fluorodeoxyglucose (FDG) PET/CT for detection of MM. Materials and Methods Participants with MM were accrued to this prospective phase 2 trial between March 2022 and July 2025. Standard-of-care ¹⁸F-FDG PET/CT and bone marrow biopsy were performed, along with research ⁸⁹Zr-DFO-daratumumab PET/CT. If there were discrepant lesions between the two scans, image-guided biopsy was considered as the reference standard. The McNemar test was used to compare disease detection between the two imaging modalities. Results This study included 60 participants (median age, 63 years [IQR, 57-71 years]; 32 women). ⁸⁹Zr-DFO-daratumumab PET/CT demonstrated at least one positive lesion in 43% (26 of 60; 95% CI: 31, 57) of participants, and ¹⁸F-FDG PET/CT demonstrated at least one positive lesion in 47% (28 of 60; 95% CI: 33, 60) of participants. While there was no overall difference in disease detection between the two imaging modalities (<i>P</i> = .81), MM was demonstrated only with ⁸⁹Zr-DFO-daratumumab PET/CT in 13% (eight of 60) of participants, with subsequent biopsy confirmation of active myeloma. Conclusion In participants with MM, CD38-targeted ⁸⁹Zr-DFO-daratumumab immuno-PET helped detect active myeloma in some participants with no signs of disease at ¹⁸F-FDG PET/CT. Clinical trial registration no. NCT04814615 &#xa9; RSNA, 2026 <i>Supplemental material is available for this article.</i> See also the editorial by Choyke in this issue.