CD38-Targeted Immuno-PET Helps Detect Active Multiple Myeloma

The investigational CD38-targeted immuno-PET tracer zirconium 89 (89Zr) deferoxamine (DFO)–daratumumab (Darzalex) detected active multiple myeloma in some patients who had no evidence of disease on standard-of-care fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT, according to results from a prospective phase 2 trial (NCT04814615) published in Radiology.¹

What did the imaging comparison show?

In the trial, 89Zr-DFO-daratumumab PET/CT demonstrated at least 1 positive lesion in 43% of patients (n = 26/60; 95% CI, 31%-57%), and 18F-FDG PET/CT demonstrated at least 1 positive lesion in 47% (n = 28/60; 95% CI, 33%-60%), with no overall difference in disease detection between the 2 modalities (P = .81). Disease was identified only on 89Zr-DFO-daratumumab PET/CT in 13% of patients (n = 8/60)—all biopsy-confirmed—and only on 18F-FDG PET/CT in 17% (n = 10/60); both scans were positive in 30% (n = 18/60) and negative in 40% (n = 24/60).

“Myeloma cells frequently consume the same amount of glucose as the surrounding normal cells,” said C. Ola Landgren, MD, PhD, professor and chief of the myeloma division, director of the Sylvester Myeloma Institute at the University of Miami Miller School of Medicine, and senior author of the study, in a news release.² “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.”

How did lesion detection and tracer uptake compare?

More sites of disease were identified with 89Zr-DFO-daratumumab PET/CT than with 18F-FDG PET/CT in 28% of patients (n = 17/60), while more sites were identified with 18F-FDG PET/CT in 22% (n = 13/60); the 2 tracers detected an equal number of lesions in the remaining 52% (n = 31/60). These findings, the investigators noted, reflect complementary information rather than one modality replacing the other.

The maximum standardized uptake value (SUVmax) of lesions was higher with 89Zr-DFO-daratumumab (mean, 22.5) than with 18F-FDG (mean, 11.5). Among 59 patients who underwent standard-of-care blind iliac bone marrow biopsy, 12 had a biopsy negative for myeloma, yet 1 or both imaging studies were positive in 9 of those 12 patients (75%), allowing confirmation of active disease despite a negative biopsy.

“Their standard tests showed no evidence of disease, but we found nearly 100 sites of myeloma throughout the body,” Landgren said.² “These are exactly the kinds of patients who benefit from better scans.”

What was the safety and feasibility profile?

No severe adverse events (AEs) were reported with 89Zr-DFO-daratumumab administration (n = 0/60). Non-severe AEs occurred in 5% of patients (n = 3/60) during administration of nonradiolabeled daratumumab—1 case of increased heart rate and 2 of cough—all of which resolved with a preplanned intervention, and no reactions prevented completion of imaging. The tracer requires a 6- to 7-day interval between administration and imaging to allow the radiolabeled antibody to circulate, and the investigators noted that heterogeneous, sometimes substantial background bone marrow uptake of 89Zr-DFO-daratumumab may have limited lesion detection in some patients. In a post hoc analysis, scans negative for malignancy had higher background bone marrow avidity than positive scans (P = .004).

What did the investigators conclude?

The authors concluded that CD38-targeted 89Zr-DFO-daratumumab immuno-PET represents a novel imaging modality for patients with multiple myeloma that may be most beneficial in those with non–FDG-avid disease. They emphasized that it is intended to add information alongside imaging, blood tests, and bone marrow biopsy rather than replace existing tools.

“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,” Landgren said.² “We are developing new and better technology designed to see where the disease is and make sure we are not missing it.”

What was the trial design, and what comes next?

The prospective, two-center phase 2 trial accrued 60 patients with multiple myeloma between March 2022 and July 2025 at Hoag Family Cancer Institute and the University of Miami. All patients had previously proven CD38-positive myeloma and were planned for first-line or a new line of therapy; each underwent both research 89Zr-DFO-daratumumab PET/CT and standard-of-care 18F-FDG PET/CT, with image-guided biopsy of discrepant lesions serving as the reference standard. The median patient age was 63 years, and 53% were women.

The investigators noted limitations including the relatively small sample size, which produced wide confidence intervals, and the lack of clinical outcome data. Next-generation versions using smaller antibody fragments that reach tumors more quickly to potentially enable a same-day test are in development, and ongoing research is evaluating 89Zr-DFO-daratumumab for detecting residual disease after treatment and predicting response to CD38-targeted therapy.

References

1. Ulaner GA, Kuker RA, Diamond B, et al. Phase 2 trial of 89Zr-deferoxamine-daratumumab for CD38-targeted immuno-PET/CT detection of multiple myeloma. Radiology. 2026;321(2):e260517. doi:10.1148/radiol.260517
2. Welsh J. Imaging the invisible: a new precision approach to detecting multiple myeloma. News release. University of Miami Miller School of Medicine. November 3, 2026. Accessed November 4, 2026. https://tinyurl.com/y2e6rss2