title: Red Marrow-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with 177Lu-Lilotomab Satetraxetan, a Novel Anti-CD37 Antibody-Radionuclide Conjugate.
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 the177Lu-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 of177Lu-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.
  
  
  CONCLUSIONS
  Predosing with lilotomab reduces the RM-absorbed dose for177Lu-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.
authors: Department of Diagnostic Physics, Oslo University Hospital, Oslo, Norway.
authors: Johan
authors: J
authors: Blakkisrud
authors: Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
authors: Ayca
authors: A
authors: Løndalen
authors: Nordic Nanovector ASA, Oslo, Norway.
authors: Jostein
authors: J
authors: Dahle
authors: Nordic Nanovector ASA, Oslo, Norway.
authors: Simon
authors: S
authors: Turner
authors: Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; and.
authors: Harald
authors: H
authors: Holte
authors: Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; and.
authors: Arne
authors: A
authors: Kolstad
authors: Department of Diagnostic Physics, Oslo University Hospital, Oslo, Norway carsto@ous-hf.no.|Department of Life Science and Health, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
authors: Caroline
authors: C
authors: Stokke
mesh_terms: D065638:Absorption, Radiation; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000951:Antigens, Neoplasm; D001853:Bone Marrow / Q000528:radiation effects*; D005260:Female; D006801:Humans; D008187:Lutetium / Q000008:administration & dosage*; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011868:Radioisotopes / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D059470:Tetraspanins / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C059071:CD37 protein, human; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D059470:Tetraspanins; D008187:Lutetium
keywords: 177Lu-lilotomab satetraxetan; antibody–radionuclide conjugate; non-Hodgkin lymphoma; red marrow–absorbed dose