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Principal Investigator: Carl Ola Landgren
Organization: HOAG MEMORIAL HOSPITAL PRESBYTERIAN
Fiscal Year: 2024
Award: $560,238
Funding agency: National Cancer Institute
Project Summary / Abstract
Multiple myeloma is a plasma cell neoplasm with poor prognosis but promising future treatment. Current
measurements of myeloma disease burden are suboptimal, and this limits clinical care. We have completed a
first-in-human trial of CD38-targeted immunoPET with the radiolabeled anti-CD38 monoclonal antibody, 89Zr-
DFO-daratumumab, which very successfully visualized myeloma disease burden as never done before. This
proposal is a phase 2 clinical trial to identify clinically valuable applications of CD38-targeted immunoPET in
patients with multiple myeloma.
Our central hypothesis is that targeted imaging of CD38, which is expressed on the surface of virtually every
myeloma cell, will allow clinically valuable non-invasive immuno-PET imaging of patients with myeloma. This
would be a transformative strategy for the measurement of myeloma tumor burden, selection of therapeutic
agents, and monitoring of treatment response.
In the first aim of the study, we will determine the correlation between tumor uptake of 89Zr-DFO-daratumumab
with clinically standard laboratory and imaging measurement of myeloma, including patient serum M protein
concentration, percentage of plasma cells on bone marrow biopsy, FDG PET/CT, and whole-body MR. Because
current approaches to assessing myeloma tumor burden are sub-optimal, developing a method to sensitively
visualize and localize myeloma could have a profound impact on patient care.
In the second aim of the study, we will determine if tumor uptake of 89Zr-DFO-daratumumab predicts response
to daratumumab-containing combination therapy. Not all patients respond to daratumumab therapy; thus, a
method of predicting response would be valuable for selection of therapy in individual patients.
In the third aim, we will determine if 89Zr-DFO-daratumumab imaging following daratumumab-containing
combination therapy can detect clinically significant residual disease. Detection of minimal residual disease
(MRD) following therapy continues to grow in importance as a prognostic marker and endpoint in myeloma
clinical trials. A method of visualizing and localizing residual disease would impact patient care, as well as
enhance trials of developing myeloma therapies.
The ultimate goal of this work would be the identification of clinically valuable applications for 89Zr-DFO-
daratumumab immunoPET and, if successful, advancement toward FDA approval of this agent.
Terms: <Antibodies><Biopsy><Blood Plasma Cell><Blood Serum><Blood Tests><Bone marrow biopsy><Cell Body><Cells><Clinical><Clinical Treatment Moab><Clinical Trials><Combined Modality Therapy><Detectable Residual Disease><Detection><Detection of Minimal Residual Disease><Disease><Disorder><Early-Stage Clinical Trials><FDG PET><Funding Opportunities><Future><Goals><Hematologic Tests><Hematological Tests><Hematology Testing><Histologic><Histologically><Human><Image><Immune Globulins><Immuno-PET><ImmunoPET><Immunoglobulins><Immunoradiotherapy><Investigation><Investigators><Laboratories><M protein><MSKCC><Measurement><Measures><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Memorial Sloan-Kettering Cancer Center><Methods><Minimal Residual Disease><Modern Man><Monitor><Monoclonal Antibodies><Multimodal Therapy><Multimodal Treatment><Multiple Myeloma><PET><PET Scan><PET imaging><PET/CT><PET/CT scan><PETSCAN><PETT><Patient Care><Patient Care Delivery><Patient Monitoring><Patient imaging><Patients><Phase><Phase 1 Clinical Trials><Phase 2 Clinical Trials><Phase I Clinical Trials><Phase II Clinical Trials><Plasma Cell Dyscrasia><Plasma Cell Neoplasm><Plasma Cell Tumor><Plasma Cells><Plasma-Cell Myeloma><Plasmacytes><Plasmacytic Neoplasm><Plasmacytic Tumour><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Prognosis><Prognostic Marker><Protein Secretion><Qualifying><Rad.-PET><Radiation Chemistry><Radiochemistry><Radioimmunotherapy><Radiolabeled><Research Personnel><Researchers><Residual Neoplasm><Residual Tumors><Safety><Selection for Treatments><Serum><Site><Surface><Surface Proteins><Therapeutic Agents><Tracer><Translations><Tumor Burden><Tumor Load><United States><Visualization><Work><blind><burden of disease><burden of illness><cancer imaging><care for patients><care of patients><caring for patients><clinical applicability><clinical application><clinical care><clinical significance><clinically significant><combination therapy><combined modality treatment><combined treatment><design><designing><disease burden><dosimetry><early phase trial><experience><first in man><first-in-human><fluorodeoxyglucose PET><fluorodeoxyglucose positron emission tomography><human imaging><image-based method><imaging><imaging agent><imaging method><imaging modality><immune-PET><individual patient><innovate><innovation><innovative><mAbs><monoclonal Abs><multi-modal therapy><multi-modal treatment><multiple myeloma M Protein><myeloma><myelomatosis><novel><oncologic imaging><oncology imaging><phase 1 trial><phase 2 trial><phase I protocol><phase I trial><phase II protocol><phase II trial><plasmocyte><positron emission computed tomography><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><pre-clinical imaging><preclinical imaging><predict responsiveness><predicting response><prognostic biomarker><radiolabeling><radiologically labeled><residual disease><response to therapy><response to treatment><selection of treatment><targeted imaging><theranostics><therapeutic response><therapy response><therapy selection><translation><treatment response><treatment responsiveness><treatment selection><tumor><tumor imaging><uptake><virtual>