Synthesis, preclinical analysis, and first-inhuman phase I imaging of 89Zr-DFOdaratumumab for CD38 targeted imaging of myeloma

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Published: 25 Sep 2019
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Prof Ola Landgren - Memorial Sloan Kettering Cancer Center, New York City, USA

Prof Ola Landgren speaks to ecancer at the 2019 International Myeloma Workshop meeting in Boston on the synthesis, preclinical analysis, and first-inhuman phase I imaging of 89Zr-DFOdaratumumab for CD38 targeted imaging of myeloma.

He explains that initially myeloma cell lines followed by an antibody were injected into mice and it was seen that the antibody binds to the cell lines and is detectable by PET scan.

Prof Landgren reports that, following the study moving into human patients, this is a safe strategy with no new toxicities.
 

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

I did present results from our work, both in the lab we have done mouse models and we have studied imaging in mouse models and we have also done a phase I study with Immuno-PET. So that was part of the presentation. We had radiolabelled daratumumab with a molecule called zirconium-89 and we first in the lab injected myeloma cell lines in mice and then we injected this antibody. We were able to show that the antibody binds to where the cell lines are located and we could detect this with PET scanners for mice in the lab, we could see the myeloma.

So that led us to continue developing this strategy into humans. We wrote the full protocol for a phase I study and we then submitted that to the FDA and obtained an IND for this. We showed, based on ten patients, that it’s a safe strategy to give this antibody. There are no surprises in terms of new toxicities beyond what you see with daratumumab as a treatment strategy, which is virtually nothing. If you pre-medicate you virtually don’t see any infusion reactions with this strategy either. We further showed that the imaging could be done five or six days after the antibody had been given. If you do it too early there will be a lot of background noise and you would have antibody circulating in the blood and it could be in different organ systems – in the liver and the spleen etc. So if you wait for 5-6 days you clearly see if there is focal uptake or not.

We also showed in only one patient, because this was the phase I study designed to study safety and feasibility, but one patient we had done a conventional FDG PET-CT which is a standard PET-CT that we normally do in the hospital and everyone is doing the same PET-CT FDG. So in a patient that had myeloma who was on the study we did a FDG PET-CT and there was no focal uptake. A week later when we did the Immuno-PET we saw that there were multiple sites of active uptake in this same patient. We did not in the phase I study have image-guided biopsy but when we look at the CT we saw that there are bone destructions at the same exact site as there is this uptake of the Immuno-PET. So that’s very encouraging for potential uptake of residual disease.

So overall we deem it safe, we deem it feasible and it’s very exciting. So we also interpret this as a signal for us to develop a phase II trial. So we are now working and probably in the coming 2-3 months we hope to open a phase II study that will include 50-60 patients where we will compare it to conventional FEG PET-CT. We will also compare it to bone marrow biopsies and bloodwork with M-spikes and light chains to see if this could be a more sensitive technology than conventional imaging, biopsies, MRD testing and blood work. So we are very excited about it and this is the first time, to my knowledge, this has been done in patients with multiple myeloma.