First exploration of the on-treatment changes in tumor and organ uptake of a radiolabeled anti PD-L1 antibody during chemoradiotherapy in patients with non-small cell lung cancer using whole body PET.

Autor:	Pouw JEE; Department of Medical Oncology, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands.; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands., Hashemi SMS; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands.; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Huisman MC; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands.; Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Wijngaarden JE; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands.; Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Slebe M; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands.; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Oprea-Lager DE; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands.; Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Zwezerijnen GJC; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands.; Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Vugts D; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands.; Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Ulas EB; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands.; Cancer Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands., de Gruijl TD; Department of Medical Oncology, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands.; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands., Radonic T; Department of Pathology, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Senan S; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands.; Department of Radiation Oncology, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Menke-van der Houven van Oordt CW; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands.; Medical Oncology, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands., Bahce I; Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Netherlands i.bahce@amsterdamumc.nl.; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2024 Feb 01; Vol. 12 (2). Date of Electronic Publication: 2024 Feb 01.
DOI:	10.1136/jitc-2023-007659
Abstrakt:	Background: In patients with locally advanced unresectable non-small cell lung cancer (NSCLC), durvalumab, an anti-programmed cell death ligand-1 (PD-L1) antibody, has shown improved overall survival when used as consolidation therapy following concurrent chemoradiotherapy (CRT). However, it is unclear whether CRT itself upregulates PD-L1 expression. Therefore, this study aimed to explore the changes in the uptake of the anti PD-L1 antibody [ 89 Zr]Zr-durvalumab in tumors and healthy organs during CRT in patients with NSCLC. Methods: Patients with NSCLC scheduled to undergo CRT were scanned 7±1 days after administration of 37±1 MBq [ 89 Zr]Zr-durvalumab at baseline, 1-week on-treatment and 1 week after finishing 6 weeks of CRT. First, [ 89 Zr]Zr-durvalumab uptake was visually assessed in a low dose cohort with a mass dose of 2 mg durvalumab (0.13% of therapeutic dose) and subsequently, quantification was done in a high dose cohort with a mass dose of 22.5 mg durvalumab (1.5% of therapeutic dose). Tracer pharmacokinetics between injections were compared using venous blood samples drawn in the 22.5 mg cohort. Visual assessment included suspected lesion detectability. Positron emission tomography (PET) uptake in tumoral and healthy tissues was quantified using tumor to plasma ratio (TPR) and organ to plasma ratio, respectively. Results: In the 2 mg dose cohort, 88% of the 17 identified tumor lesions were positive at baseline, compared with 69% (9/13) for the 22.5 mg cohort. Although the absolute plasma concentrations between patients varied, the intrapatient variability was low. The ten quantitatively assessed lesions in the 22.5 mg cohort had a median TPR at baseline of 1.3 (IQR 0.7-1.5), on-treatment of 1.0 (IQR 0.7-1.4) and at the end of treatment of 0.7 (IQR 0.6-0.7). On-treatment, an increased uptake in bone marrow was seen in three out of five patients together with a decreased uptake in the spleen in four out of five patients. Conclusions: This study successfully imaged patients with NSCLC with [ 89 Zr]Zr-durvalumab PET before and during CRT. Our data did not show any increase in [ 89 Zr]Zr-durvalumab uptake in the tumor 1-week on-treatment and at the end of treatment. The changes observed in bone marrow and spleen may be due to an CRT-induced effect on immune cells. Trial Registration Number: EudraCT number: 2019-004284-51. Competing Interests: Competing interests: SMSH is on the advisory board and/or received institutional research support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche and Takeda. DV received institutional research support from Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Boehringer Ingelheim, Roche and Aplagon. SS is on the advisory board of AstraZeneca, receives institutional research support and a speakers fee from AstraZeneca. SS is on the advisory board of Bristol-Myers Squibb and receives institutional research support from Bristol-Myers Squibb. CWM-vdHvO is advisor for GEHealthcare and Eli Lilly and received institutional research support from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, G1 Therapeutics and Bristol-Myers Squibb. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu