A phase 2 trial of 89Zr-DFO-daratumumab for CD38-targeted imaging of multiple myeloma (the iMMunoPET study)

Abstract Background Evaluation of multiple myeloma disease burden and response to therapy are currently suboptimal. For instance, ~30% of myeloma lytic bone lesions are not detected by standard FDG PET imaging. This limits treatment planning and evaluation of residual disease following treatment. 89Zr-DFO-daratumumab is a novel immunoPET tracer that is designed to detect CD38 on myeloma cells and allow visualization of myeloma on PET. A phase I study of 89Zr-DFO-daratumumab demonstrated safety and successful visualization of myeloma with 89Zr-DFO-daratumumab. Here, we detail the fully enrolled phase II study of 89Zr-DFO-daratumumab for the imaging of MM (the iMMunoPET study). Methods This phase II trial, performed on an NIH R01 grant, is designed for 60 participants with multiple myeloma and a plan for a change in systemic therapy. Prior to therapy, FDG PET/CT and bone marrow biopsy are performed as standard-of-care, as well as research 89Zr-DFO-daratumumab PET/CT. If there are discrepant lesions between the 2 scans, biopsy was performed for reference standard. Participants then undergo standard-of-care therapy for multiple myeloma. Upon suspected recurrence or completion of 1 year of therapy, FDG PET/CT, bone marrow biopsy, and 89Zr-DFO-daratumumab PET/CT are repeated. This design will determine how 89Zr-DFO-daratumumab immunoPET compares with current methods for measuring and localizing MM disease prior to therapy and for detecting residual disease after therapy. Results The full cohort of 60 participants has been accrued. In 16 (27%) patients, 89Zr-DFO-daratumumab PET/CT identified more sites of disease than FDG PET/CT, including 7 patients where disease was only detected on 89Zr-DFO-daratumumab PET/CT (Figure). In 13 (22%) participants, FDG PET/CT identified more sites of disease than 89Zr-DFO-daratumumab PET/CT. In the remaining 31 (51%) participants, disease detection was equal between the two agents. Conclusions In this immune-based targeted imaging Phase 2 studyfor multiple myeloma, we found thatCD38-targeted immunoPET with 89Zr-DFO-daratumumab PET/CT successfully identifies and localizes active myeloma disease, even in some patients where the myeloma cells are not FDG-avid. In ~30% of the participants, 89Zr-DFO-daratumumab PET/CT identified more sites of disease than FDG PET/CT, including 7 patients where disease was only detected on 89Zr-DFO-daratumumab. In two cases that were negative by standard-of-care FDG PET/CT, we found more than 100 sites of detectable disease using 89Zr-DFO-daratumumab PET/CT. We conclude that, in some participants, targeted immunoPET-based imaging has higher sensitivity compared to metabolic-based standard-of-care FDG PET/CT. Using data from this fully enrolled study, we will provide head-to-head comparisons of 89Zr-DFO-daratumumab PET/CT, standard-of-care FDG PET/CT, bone marrow biopsy, and serum protein markers at the meeting (clinicaltrials.gov, NCT04814615).