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

Ayca Løndalen, Johan Blakkisrud, Mona-Elisabeth Revheim, Ulf Erik Madsbu, Jostein Dahle, Arne Kolstad, Caroline Stokke, Ayca Løndalen, Johan Blakkisrud, Mona-Elisabeth Revheim, Ulf Erik Madsbu, Jostein Dahle, Arne Kolstad, Caroline Stokke

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.

Keywords: 177Lu-lilotomab satetraxetan; FDG PET/CT; Non-Hodgkin lymphoma; Radioimmunotherapy; Tumor dosimetry.

Conflict of interest statement

Arne Kolstad were both in part supported by grants from the Norwegian Cancer Society. Arne Kolstad is member of the Scientific Advisory Board of Nordic Nanovector ASA. Jostein Dahle is an employee and shareholder of Nordic Nanovector ASA. Ayca Løndalen has no conflict of interest. Johan Blakkisrud has no conflict of interest. Mona-Elisabeth Revheim has no conflict of interest. Ulf Erik Madsbu has no conflict of interest. Caroline Stokke has no conflict of interest.

Figures

Fig. 1
Fig. 1
Study design: 3 different dosage levels, 10, 15, or 20 MBq/kg, were investigated in five arms of the phase 1/2a trial. Different pre-dosing regimens were given 1–3 h before 177Lu-lilotomab satetraxetan injection, except for arm 2. Pre-treatment regimens were given 28 and 21 days or 14 days before. FDG PET and ceCT were performed as baseline investigations and for response evaluation. The 0-h time point on the grey time line indicates administration of 177Lu-lilotomab satetraxetan
Fig. 2
Fig. 2
Imaging protocols: FDG PET was performed at baseline (PETbaseline), within 2 weeks of the first pre-treatment. It was repeated for response evaluation at 3 months and at 6 months. Baseline ceCT was performed within 2 weeks of the start of pre-treatment and repeated at 3, 6, 9, and 12 months, 2–3 times after 1–2 years and once 2–5 years after 177Lu lilotomab satetraxetan treatment. SPECT/CT imaging was performed at days 1, 4, and 7 (expect for in arm 1, where only day 4 and 7 SPECT/CT was performed) and used for dosimetry calculations. The 0-h time point indicates administration of 177Lu-lilotomab satetraxetan
Fig. 3
Fig. 3
Images obtained at baseline and response evaluation, as well as SPECT/CT images showing the uptake of 177Lu-lilotomab satetraxetan at one time point. CTbaseline, PETbaseline, SPECT day 4, PET3months, and CT6months for a patient 17, b patient 21, and c patient 16
Fig. 4
Fig. 4
Tumor-absorbed doses plotted against a ΔSUVmax-3months (%), b ΔSUVmax-6months (%),c ΔMTV3months (%),d ΔTLG3months (%), e ΔCT6months (%), and f ΔCT12months (%). Each symbol represents a lesion, different symbols represents arms, as shown in legend. No clear overall correlations were found between tumor-absorbed doses and change in FDG PET and ceCT parameters
Fig. 5
Fig. 5
Tumor-absorbed doses for responders and non-responders: a Measured at PET3months. b Measured at PET6months
Fig. 6
Fig. 6
Baseline SUVmaxa and tumor volume at start of treatment b plotted against tumor-absorbed dose. Tumor volume in b is plotted on a logarithmic scale. There was no correlation between baseline SUVmax or tumor volume and tumor-absorbed dose
Fig. 7
Fig. 7
Tumor-absorbed doses plotted against ΔSUVmax-3months in a arm 1, b arm 2, c arm 3, and d arms 4 + 5. In each panel, different color and symbol codings represent individual patients, and each symbol represents an individual tumor lesion. The lines represent correlation between ΔSUVmax-3months and dose for tumors in individual patients. Interpatient variability in radiosensitivity is here evident, and intra-patient dose-response relationships also appear for most patients

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