FDG PET/CT and Dosimetric Studies of 177Lu-Lilotomab Satetraxetan in a First-in-Human Trial for Relapsed Indolent non-Hodgkin Lymphoma-Are We Hitting the Target?

Ayca Løndalen; Johan Blakkisrud; Mona-Elisabeth Revheim; Jostein Dahle; Arne Kolstad; Caroline Stokke

doi:10.1007/s11307-022-01731-3

FDG PET/CT and Dosimetric Studies of ¹⁷⁷Lu-Lilotomab Satetraxetan in a First-in-Human Trial for Relapsed Indolent non-Hodgkin Lymphoma-Are We Hitting the Target?

Mol Imaging Biol. 2022 Oct;24(5):807-817. doi: 10.1007/s11307-022-01731-3. Epub 2022 Apr 29.

Authors

Ayca Løndalen^{1

2}, Johan Blakkisrud^{3

4}, Mona-Elisabeth Revheim^{3

5}, Jostein Dahle⁶, Arne Kolstad⁷, Caroline Stokke^{3

4}

Affiliations

¹ Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway. ayca.londalen@getmail.no.
² Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. ayca.londalen@getmail.no.
³ Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
⁴ Department of Physics, University of Oslo, Oslo, Norway.
⁵ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁶ Nordic Nanovector ASA, Oslo, Norway.
⁷ Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway.

Abstract

Purpose: [¹⁷⁷Lu]Lu-lilotomab satetraxetan, a novel CD37 directed radioimmunotherapy (RIT), has been investigated in a first-in-human phase 1/2a study for relapsed indolent non-Hodgkin lymphoma. In this study, new methods were assessed to calculate the mean absorbed dose to the total tumor volume, with the aim of establishing potential dose-response relationships based on 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) parameters and clinical response. Our second aim was to study if higher total tumor burden induces reduction in the ¹⁷⁷Lu-lilotomab satetraxetan accumulation in tumor.

Procedures: Fifteen patients with different pre-dosing (non-radioactive lilotomab) regimens were included and the cohort was divided into low and high non-radioactive lilotomab pre-dosing groups for some of the analyses. ¹⁷⁷Lu-lilotomab satetraxetan was administered at dosage levels of 10, 15, or 20 MBq/kg. Mean absorbed doses to the total tumor volume (tTAD) were calculated from posttreatment single-photon emission tomography (SPECT)/computed tomography (CT) acquisitions. Total values of metabolic tumor volume (tMTV), total lesion glycolysis (tTLG) and the percent change in these parameters were calculated from FDG PET/CT performed at baseline, and at 3 and 6 months after RIT. Clinical responses were evaluated at 6 months as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).

Results: Significant decreases in tMTV and tTLG were observed at 3 months for patients receiving tTAD ≥ 200 cGy compared to patients receiving tTAD < 200 cGy (p = .03 for both). All non-responders had tTAD < 200 cGy. Large variations in tTAD were observed in responders. Reduction in ¹⁷⁷Lu-lilotomab satetraxetan uptake in tumor volume was not observed in patients with higher baseline tumor burden (tTMV).

Conclusion: tTAD of ≥ 200 cGy may prove valuable to ensure clinical response, but further studies are needed to confirm this in a larger patient population. Furthermore, this work indicates that higher baseline tumor burden (up to 585 cm³) did not induce reduction in radioimmunoconjugate accumulation in tumor.

Keywords: FDG PET/CT; Indolent non-Hodgkin lymphoma; Radioimmunotherapy; SPECT/CT; Tumor absorbed dose.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / therapeutic use
Fluorodeoxyglucose F18
Glucose
Humans
Immunoconjugates*
Lymphoma, Non-Hodgkin* / diagnostic imaging
Lymphoma, Non-Hodgkin* / drug therapy
Lymphoma, Non-Hodgkin* / radiotherapy
Positron Emission Tomography Computed Tomography

Substances

(177)Lu-lilotomab satetraxetan
Antineoplastic Agents
Fluorodeoxyglucose F18
Glucose
Immunoconjugates