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

Overview

Journal Mol Imaging Biol

Publisher Springer

Specialties Molecular Biology
Radiology

Date 2022 Apr 29

PMID 35486292

Authors

Ayca Londalen

Johan Blakkisrud

Mona-Elisabeth Revheim

Jostein Dahle

Arne Kolstad

Caroline Stokke

Affiliations

Soon will be listed here.

Abstract

Purpose: [Lu]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 Lu-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. Lu-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 Lu-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 cm) did not induce reduction in radioimmunoconjugate accumulation in tumor.

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