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

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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?

10.21203/rs.3.rs-442683/v1 ◽

2021 ◽

Author(s):

Ayca Løndalen ◽

Johan Blakkisrud ◽

Mona-Elisabeth Revheim ◽

Jostein Dahle ◽

Arne Kolstad ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Dose Response ◽

Fdg Pet ◽

Tumor Tissue ◽

Absorbed Dose ◽

Non Hodgkin Lymphoma ◽

Absorbed Doses ◽

Pet Ct ◽

Clinical Responses ◽

Fdg Pet Ct

Abstract Purpose: 177Lu-lilotomab satetraxetan, a novel CD37 directed radioimmunotherapy (RIT), has been investigated in a first-in-human phase 1/2a study for relapsed non-Hodgkin lymphoma (NHL). Absorbed dose for all tumor tissue in the body is a crucial parameter in RIT which has traditionally been challenging to calculate. The aim of this study was to investigate the correlations between baseline FDG PET/CT and posttreatment SPECT/CT parameters, absorbed dose-response relationships and clinical responses.Materials and methods: A total of 15 patients with different pre-treatment and pre-dosing regimens were included. 177Lu-lilotomab satetraxetan was administered at dosage levels of 10, 15 or 20 MBq/kg. Total radioimmunoconjugate tumor volume (tRTV), total radioimmunoconjugate lesion uptake (tRLU) and total tumor absorbed dose (tTAD) were calculated from posttreatment SPECT/CT. The measured uptake values and absorbed doses were normalized for dosage when appropriate. For some of the analyses, the cohort was divided into low (arm 1) and high (arm 4+5) non-radioactive lilotomab pre-dosing groups. tMTV and tTLG were calculated from FDG PET/CT performed at baseline, 3 and 6 months after RIT, and the percent change for these parameters calculated (∆tMTV3months, ∆tTLG3months and ∆tMTV6months, ∆tTLG6months). Clinical responses were evaluated at 6 months.Results: tTMV and tRTV were significantly correlated (p<0.01). A correlation was also found between tTLG and tRLU (p<0.01). Correlations were not observed between baseline tTMV and tTAD. Decreases in ∆tMTV and ∆tTLG were significantly higher at PET3months for patients receiving tTAD≥200cGy compared to patients receiving lower tumor absorbed doses (p=.03 for both). Also, significant decreases in ∆tMTV3months, ∆tTLG3months and ∆tMTV6months, ∆tTLG6months were observed with increasing tTAD in the high lilotomab patient group. Similarly, responders (patients with complete remission and partial remission) had higher mean tTAD compared to non-responders (stable disease and progressive disease). This was statistically significant in the high lilotomab group. Across the entire population, all non-responders had tTAD < 200cGy, and all patients with tTAD ≥ 200cGy were responders.Conclusion: This work indicates that 177Lu-lilotomab satetraxetan targets FDG avid lesions, and that increasing baseline (tMTV) does not have a decreasing effect on the total tumor absorbed dose (tTAD). The patient group receiving a higher amount of lilotomab pre-dosing demonstrated an absorbed dose–response relationship. Similar results were not observed in the low lilotomab group, which were expected since an overall very good response rate could mask such a relationship for this group. Regardless of pre-dosing, a mean absorbed dose to the total tumor tissue (tTAD) limit of 200cGy may prove valuable to separate clinical non-responders from responders.

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FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma: results from the prospective, multicenter PETAL and OPTIMAL>60 trials

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05348-6 ◽

2021 ◽

Author(s):

Dominic Kaddu-Mulindwa ◽

Bettina Altmann ◽

Gerhard Held ◽

Stephanie Angel ◽

Stephan Stilgenbauer ◽

...

Keyword(s):

Bone Marrow ◽

B Cell ◽

Hodgkin Lymphoma ◽

Predictive Value ◽

Fdg Pet ◽

Bone Marrow Involvement ◽

Non Hodgkin Lymphoma ◽

Pet Ct ◽

Fdg Pet Ct ◽

Initial Staging

Abstract Purpose Fluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB). Methods Patients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy. Results Among 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32–45%) and 84% (CI: 78–88%), specificity 100% (CI: 99–100%) and 100% (CI: 99–100%), positive predictive value 100% (CI: 96–100%) and 100% (CI: 98–100%), and negative predictive value 84% (CI: 81–86%) and 95% (CI: 93–97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management. Conclusion In patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted. Trial registration NCT00554164 and NCT01478542

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