Abstract
Red bone marrow (RM) is often the primary organ at risk in radioimmunotherapy; irradiation of marrow may induce short and long term hematological toxicity. 177Lu-lilotomab satetraxetan is a novel anti-CD37 antibody-radionuclide-conjugate (ARC) currently in phase 1/2a. Two pre-dosing regimens have been investigated, one with 40 mg 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 hematological toxicity. Methods: Eight patients with relapsed CD37+ indolent B-cell non-Hodgkin’s lymphoma were included for RM dosimetry. Hybrid Single Photon Emission Computed Tomography (SPECT) and Computed Tomography (CT) images were used to estimate activity concentration in the RM of lumbar L2-L4. Pharmacokinetic parameters were calculated after measurement of 177Lu-lilotomab satetraxetan concentration in blood samples. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: The mean absorbed doses to RM were 0.94 mGy/MBq for arm 1 (lilotomab+) and 1.53 mGy/MBq for arm 2 (lilotomab-). There was a statistically significant difference between arm 1 and 2 (student t-test, P = 0.02). Total RM absorbed doses ranged from 67 to 124 cGy in arm 1 and from 158 to 207 cGy in arm 2. For blood, the area under the curve (AUCblood) was higher with lilotomab pre-dosing compared to without pre-dosing (P = 0.001), while 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: Pre-dosing 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. Hematological 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.
- Oncology: Lymphoma
- Radiobiology/Dosimetry
- Radionuclide Therapy
- 177Lu-lilotomab satetraxetan
- Red marrow absorbed dose
- antibody radionuclide conjugate
- non-Hodgkins lymphoma
- Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.