FDG PET/CT parameters and correlations with tumor-absorbed doses in a phase 1 trial of 177Lu-lilotomab satetraxetan for treatment of relapsed non-Hodgkin lymphoma

Abstract

Purpose 177Lu-lilotomab satetraxetan targets the CD37 antigen and has been investigated in a first-in-human phase 1/2a study for relapsed non-Hodgkin lymphoma (NHL). Tumor dosimetry and response evaluation can be challenging after radioimmunotherapy (RIT). Changes in FDG PET/CT parameters after RIT and correlations with tumor-absorbed doses has not been examined previously in patients with lymphoma. Treatment-induced changes were measured at FDG PET/CT and ceCT to evaluate response at the lesion level after treatment, and correlations with tumor-absorbed doses were investigated. Methods Forty-five tumors in 16 patients, with different pre-treatment and pre-dosing regimens, were included. Dosimetry was performed based on multiple SPECT/CT images. FDG PET/CT was performed at baseline and at 3 and 6 months. SUVmax, MTV, TLG, and changes in these parameters were calculated for each tumor. Lesion response was evaluated at 3 and 6 months (PET3months and PET6months) based on Deauville criteria. Anatomical changes based on ceCT at baseline and at 6 and 12 months were investigated by the sum of perpendiculars (SPD). Results Tumor-absorbed doses ranged from 35 to 859 cGy. Intra- and interpatient variations were observed. Mean decreases in PET parameters from baseline to 3 months were ΔSUVmax-3months 61%, ΔMTV3months 80%, and ΔTLG3months 77%. There was no overall correlation between tumor-absorbed dose and change in FDG PET or ceCT parameters at the lesion level or significant difference in tumor-absorbed doses between metabolic responders and non-responders after treatment. Conclusion Our analysis does not show any correlation between tumor-absorbed doses and changes in FDG PET or ceCT parameters for the included lesions. The combination regimen, including cold antibodies, may be one of the factors precluding such a correlation. Increased intra-patient response with increased tumor-absorbed doses was observed for most patients, implying individual variations in radiation sensitivity or biology. Trial registration ClinicalTrials.gov Identifier (NCT01796171). Registered December 2012

Total Tumor Uptake and Absorbed Dose of 177Lu-Lilotomab Satetraxetan in a First in Human Trial for Relapsed Non-Hodgkin Lymphoma - Are We Hitting the Target?

“…This proposed effect was supported in this study by slightly higher tTAD dosage in the high lilotomab group, even though this was not signi cant. Larger tTAD dosage variations were also observed in the high lilotomab group, in line with our previous lesion based tumor absorbed dose analysis [30].…”

“…We have previously investigated lesion-based tumor absorbed doses and dose-response relationships, with analyses including 1-5 lesions per patient [30]. The criteria for lesion inclusion were then strictly de ned to allow for precise individual dosimetry of each tumor.…”

“…The criteria for lesion inclusion were then strictly de ned to allow for precise individual dosimetry of each tumor. Signi cant intra-patient variations were observed and absorbed dose-response relationship at lesion level could not be demonstrated based on changes in FDG PET parameters and Deauville 5-point-scale [30]. By measuring tTAD we here averaged out intra-patient variations and most importantly avoided possible selection bias.…”

89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma

“…In a recent study, response at the tumor lesion level after treatment with 177 Lu-lilotomab satetraxetan was evaluated by FDG PET/CT and did not correlate with tumor-absorbed dose 11 . They hypothesized that the combination regimen of radiolabeled and cold antibodies might preclude such a correlation.…”

“…Dosimetry for organs-at-risk in 177 Lu radionuclide therapy is often calculated using single photon emission computed tomography (SPECT)/computed tomography (CT) imaging. Still, this procedure has limited sensitivity and quantitative evaluation of target-mediated uptake can be challenging 10 , 11 .…”