Johan Blakkisrud1, Ayca Løndalen2, Jostein Dahle3, Simon Turner3, Harald Holte4, Arne Kolstad4, Caroline Stokke5,6. 1. Department of Diagnostic Physics, Oslo University Hospital, Oslo, Norway. 2. Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway. 3. Nordic Nanovector ASA, Oslo, Norway. 4. Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; and. 5. Department of Diagnostic Physics, Oslo University Hospital, Oslo, Norway carsto@ous-hf.no. 6. Department of Life Science and Health, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
Abstract
Red marrow (RM) is often the primary organ at risk in radioimmunotherapy; irradiation of marrow may induce short- and long-term hematologic toxicity. 177Lu-lilotomab satetraxetan is a novel anti-CD37 antibody-radionuclide conjugate currently in phase 1/2a. Two predosing regimens have been investigated, one with 40 mg of unlabeled lilotomab antibody (arm 1) and one without (arm 2). The aim of this work was to compare RM-absorbed doses for the two arms and to correlate absorbed doses with hematologic toxicity. METHODS: Eight patients with relapsed CD37+ indolent B-cell non-Hodgkin lymphoma were included for RM dosimetry. Hybrid SPECT and CT images were used to estimate the activity concentration in the RM of L2-L4. Pharmacokinetic parameters were calculated after measurement of the 177Lu-lilotomab satetraxetan concentration in blood samples. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The mean absorbed doses to RM were 0.9 mGy/MBq for arm 1 (lilotomab+) and 1.5 mGy/MBq for arm 2 (lilotomab-). There was a statistically significant difference between arms 1 and 2 (Student t test, P = 0.02). Total RM-absorbed doses ranged from 67 to 127 cGy in arm 1 and from 158 to 207 cGy in arm 2. For blood, the area under the curve was higher with lilotomab predosing than without (P = 0.001), whereas the volume of distribution and the clearance of 177Lu-lilotomab satetraxetan was significantly lower (P = 0.01 and P = 0.03, respectively). Patients with grade 3/4 thrombocytopenia had received significantly higher radiation doses to RM than patients with grade 1/2 thrombocytopenia (P = 0.02). A surrogate, non-imaging-based, method underestimated the RM dose and did not show any correlation with toxicity. CONCLUSION: Predosing with lilotomab reduces the RM-absorbed dose for 177Lu-lilotomab satetraxetan patients. The decrease in RM dose could be explained by the lower volume of distribution. Hematologic toxicity was more severe for patients receiving higher absorbed radiation doses, indicating that adverse events possibly can be predicted by the calculation of absorbed dose to RM from SPECT/CT images.
Red marrow (RM) is often the primary organ at risk in radioimmunotherapy; irradiation of marrow may induce short- and long-term hematologic toxicity. 177Lu-lilotomab satetraxetan is a novel anti-CD37 antibody-radionuclide conjugate currently in phase 1/2a. Two predosing regimens have been investigated, one with 40 mg of unlabeled lilotomab antibody (arm 1) and one without (arm 2). The aim of this work was to compare RM-absorbed doses for the two arms and to correlate absorbed doses with hematologic toxicity. METHODS: Eight patients with relapsed CD37+ indolent B-cell non-Hodgkin lymphoma were included for RM dosimetry. Hybrid SPECT and CT images were used to estimate the activity concentration in the RM of L2-L4. Pharmacokinetic parameters were calculated after measurement of the 177Lu-lilotomab satetraxetan concentration in blood samples. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The mean absorbed doses to RM were 0.9 mGy/MBq for arm 1 (lilotomab+) and 1.5 mGy/MBq for arm 2 (lilotomab-). There was a statistically significant difference between arms 1 and 2 (Student t test, P = 0.02). Total RM-absorbed doses ranged from 67 to 127 cGy in arm 1 and from 158 to 207 cGy in arm 2. For blood, the area under the curve was higher with lilotomab predosing than without (P = 0.001), whereas the volume of distribution and the clearance of 177Lu-lilotomab satetraxetan was significantly lower (P = 0.01 and P = 0.03, respectively). Patients with grade 3/4 thrombocytopenia had received significantly higher radiation doses to RM than patients with grade 1/2 thrombocytopenia (P = 0.02). A surrogate, non-imaging-based, method underestimated the RM dose and did not show any correlation with toxicity. CONCLUSION: Predosing with lilotomab reduces the RM-absorbed dose for 177Lu-lilotomab satetraxetanpatients. The decrease in RM dose could be explained by the lower volume of distribution. Hematologic toxicity was more severe for patients receiving higher absorbed radiation doses, indicating that adverse events possibly can be predicted by the calculation of absorbed dose to RM from SPECT/CT images.
Authors: Danique Giesen; Marjolijn N Lub-de Hooge; Marcel Nijland; Helen Heyerdahl; Jostein Dahle; Elisabeth G E de Vries; Martin Pool Journal: Sci Rep Date: 2022-04-15 Impact factor: 4.379
Authors: Arne Kolstad; Tim Illidge; Nils Bolstad; Signe Spetalen; Ulf Madsbu; Caroline Stokke; Johan Blakkisrud; Ayca Løndalen; Noelle O'Rourke; Matthew Beasley; Wojciech Jurczak; Unn-Merete Fagerli; Michal Kaščák; Mike Bayne; Aleš Obr; Jostein Dahle; Lisa Rojkjaer; Veronique Pascal; Harald Holte Journal: Blood Adv Date: 2020-09-08
Authors: Caroline Stokke; Johan Blakkisrud; Ayca Løndalen; Jostein Dahle; Anne C T Martinsen; Harald Holte; Arne Kolstad Journal: Eur J Nucl Med Mol Imaging Date: 2018-02-22 Impact factor: 9.236