TY - JOUR
T1 - 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
AU - Pouw, Johanna E E
AU - Hashemi, Sayed M S
AU - Huisman, Marc C
AU - Wijngaarden, Jessica E
AU - Slebe, Maarten
AU - Oprea-Lager, Daniela E
AU - Zwezerijnen, Gerben J C
AU - Vugts, Danielle
AU - Ulas, Ezgi B
AU - de Gruijl, Tanja D
AU - Radonic, Teodora
AU - Senan, Suresh
AU - Menke-van der Houven van Oordt, C Willemien
AU - Bahce, Idris
N1 - Publisher Copyright: © 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.
PY - 2024/2/1
Y1 - 2024/2/1
N2 - 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.
AB - 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.
KW - Immune Checkpoint Inhibitors
KW - Non-Small Cell Lung Cancer
KW - Programmed Cell Death 1 Receptor
KW - Radiotherapy
KW - Tumor Microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85183828800&partnerID=8YFLogxK
U2 - 10.1136/jitc-2023-007659
DO - 10.1136/jitc-2023-007659
M3 - Article
C2 - 38302416
SN - 2051-1426
VL - 12
JO - Journal for Immunotherapy of Cancer
JF - Journal for Immunotherapy of Cancer
IS - 2
M1 - e007659
ER -