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dc.contributor.authorStokke, Caroline
dc.contributor.authorBlakkisrud, Johan
dc.contributor.authorLøndalen, Ayca
dc.contributor.authorDahle, Jostein
dc.contributor.authorMartinsen, Anne Catrine Trægde
dc.contributor.authorHolte, Harald
dc.contributor.authorKolstad, Arne
dc.date.accessioned2019-02-07T14:02:43Z
dc.date.accessioned2019-03-19T11:12:43Z
dc.date.available2019-02-07T14:02:43Z
dc.date.available2019-03-19T11:12:43Z
dc.date.issued2018-02-22
dc.identifier.citationStokke C, Blakkisrud J, Løndalen AL, Dahle J, Martinsen ACT, Holte H, Kolstad A. Pre-dosing with lilotomab prior to therapy with 177Lu-lilotomab satetraxetan significantly increases the ratio of tumor to red marrow absorbed dose in non-Hodgkin lymphoma patients. European Journal of Nuclear Medicine and Molecular Imaging. 2018;45(7):1233-1241en
dc.identifier.issn1619-7070
dc.identifier.urihttps://hdl.handle.net/10642/6797
dc.description.abstractPurpose: 177Lu-lilotomab satetraxetan is a novel anti-CD37 antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma (NHL). Four arms with different combinations of pre-dosing and pre-treatment have been investigated in a first-inhuman phase 1/2a study for relapsed CD37+ indolent NHL. The aim of this work was to determine the tumor and normal tissue absorbed doses for all four arms, and investigate possible variations in the ratios of tumor to organs-at-risk absorbed doses. Methods: Two of the phase 1 arms included cold lilotomab pre-dosing (arm 1 and 4; 40 mg fixed and 100 mg/m2 BSA dosage, respectively) and two did not (arms 2 and 3). All patients were pre-treated with different regimens of rituximab. The patients received either 10, 15, or 20 MBq 177Lu-lilotomab satetraxetan per kg body weight. Nineteen patients were included for dosimetry, and a total of 47 lesions were included. The absorbed doses were calculated from multiple SPECT/CT-images and normalized by administered activity for each patient. Two-sided Student’s t tests were used for all statistical analyses. Results: Organs with distinct up take of 177Lu-lilotomab satetraxetan, in addition to tumors, were red marrow (RM), liver, spleen, and kidneys. The mean RM absorbed doses were 0.94, 1.55, 1.44, and 0.89 mGy/MBq for arms 1–4, respectively. For the patients not pre-dosed with lilotomab (arms 2 and 3 combined) the mean RM absorbed dose was 1.48 mGy/MBq, which was significantly higher than for both arm 1 (p=0.04) and arm 4 (p=0.02). Of the other organs, the highest uptakewas found in the spleen, and there was a significantly lower spleen absorbed dose for arm-4 patients than for the patient group without lilotomab pre-dosing (1.13 vs. 3.20 mGy/MBq; p<0.01). Mean tumor absorbed doses were 2.15,2.31, 1.33, and 2.67m Gy/MBq for arms1–4, respectively. After averaging the tumor absorbed dose for each patient, the patient mean tumor absorbed dose to RM absorbed dose ratios were obtained, given mean values of 1.07 for the patient group not pre-dosed with lilotomab, of 2.16 for arm 1, and of 4.62 for arm 4. The ratios were significantly higher in both arms 1 and 4 compared to the group without pre-dosing (p=0.05andp=0.02). No statistically significant difference between arms 1 and 4 was found. Conclusions: RM is the primary dose-limiting organ for 177Lu-lilotomab satetraxetan treatment, and pre-dosing with lilotomab has a mitigating effect on RM absorbed dose. Increasing the amount of lilotomab from 40 mg to 100 mg/m2 was found to slightly decrease the RM absorbed dose and increase the ratio of tumor to RM absorbed dose. Still, both pre-dosing amounts resulted in significantly higher tumor to RM absorbed dose ratios. The findings encourage continued use of pre-dosing with lilotomab.en
dc.description.sponsorshipThe LYMRIT37-01 study is sponsored by Nordic Nanovector ASA.en
dc.language.isoenen
dc.publisherSpringer Verlagen
dc.relation.ispartofseriesEuropean Journal of Nuclear Medicine and Molecular Imaging;July 2018, Volume 45, Issue 7
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectNon-Hodgkin lymphomasen
dc.subjectAntibody radionuclide conjugate therapiesen
dc.subjectRadioimmunotherapyen
dc.subjectMolecular radiotherapyen
dc.subjectDosimetriesen
dc.subject177Lu-lilotomab satetraxetanen
dc.titlePre-dosing with lilotomab prior to therapy with 177Lu-lilotomab satetraxetan significantly increases the ratio of tumor to red marrow absorbed dose in non-Hodgkin lymphoma patientsen
dc.typeJournal articleen
dc.typePeer revieweden
dc.date.updated2019-02-07T14:02:43Z
dc.description.versionpublishedVersionen
dc.identifier.doihttp://dx.doi.org/10.1007/s00259-018-3964-9
dc.identifier.cristinID1597672
dc.source.issn1619-7070
dc.source.issn1619-7089
dc.relation.journalEuropean Journal of Nuclear Medicine and Molecular Imaging


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This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Except where otherwise noted, this item's license is described as This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.