Identifying CD381 cells in patients with multiple myeloma: First-in-human imaging using copper-64–labeled daratumumab

Amrita Krishnan, Vikram Adhikarla, Erasmus K. Poku, Joycelynne Palmer, Ammar Chaudhry, Van Eric Biglang-Awa, Nicole Bowles, Nitya Nathwani, Michael Rosenzweig, Firoozeh Sahebi, Chatchada Karanes, Jennifer Simpson, James F. Sanchez, Dave Yamauchi, Maria Parayno, Arnab Chowdhury, Enrico Caserta, Guido Marcucci, Russell Rockne, Anna M. WuJeffrey Wong, Stephen J. Forman, David Colcher, Paul Yazaki, John Shively, Flavia Pichiorri

Research output: Contribution to journalArticlepeer-review

Abstract

18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/ CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n 5 3), 10 (n 5 3), 45 (n 5 3), or 95 mg (n 5 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.

Original languageEnglish (US)
Pages (from-to)5194-5202
Number of pages9
JournalBlood Advances
Volume4
Issue number20
DOIs
StatePublished - Oct 23 2020
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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