Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate ¹⁷⁷Lu-Lilotomab Satetraxetan

Abstract

177 Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate currently tested in a phase 1/2a first-in-human dosage escalation trial for patients with relapsed CD371 indolent non-Hodgkin lymphoma. The aim of this work was to develop dosimetric methods and calculate tumor-absorbed radiation doses for patients treated with 177 Lu-lilotomab satetraxetan. Methods: Patients were treated at escalating injected activities (10, 15 and 20 MBq/kg) of 177 Lulilotomab satetraxetan and with different predosing, with or without 40 mg of unlabeled lilotomab. Eight patients were included for the tumor dosimetry study. Tumor radioactivity concentrations were calculated from SPECT acquisitions at multiple time points, and tumor masses were delineated from corresponding CT scans. Tumor-absorbed doses were then calculated using the OLINDA sphere model. To perform voxel dosimetry, the SPECT/CT data and an inhouse-developed MATLAB program were combined to investigate the dose rate homogeneity. Results: Twenty-six tumors in 8 patients were ascribed a mean tumor-absorbed dose. Absorbed doses ranged from 75 to 794 cGy, with a median of 264 cGy across different dosage levels and different predosing. A significant correlation between the dosage level and tumor-absorbed dose was found. Twenty-one tumors were included for voxel dosimetry and parameters describing dose-volume coverage calculated. The investigation of intratumor voxel doses indicates that mean tumor dose is correlated to these parameters. Conclusion: Tumor-absorbed doses for patients treated with 177 Lu-lilotomab satetraxetan are comparable to doses reported for other radioimmunotherapy compounds. Although the intertumor variability was considerable, a correlation between tumor dose and patient dosage level was found. Our results indicate that mean dose may be used as the sole dosimetric parameter on the lesion level.

Red Marrow–Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with 177Lu-Lilotomab Satetraxetan, a Novel Anti-CD37 Antibody–Radionuclide Conjugate

“…This is in accordance with our finding that absorbed dose in tumors significantly increased with patient dosage level (1).…”

“…Vertebrae L2-L4 were chosen to quantify activity using SPECT/ CT images as previously described for tumors (1). The mass of the marrow in L2-L4 was estimated for each patient by drawing a volume of interest defining the interior space of the corpus vertebrae.…”

“…The SPECT/CT imaging protocol has been described previously (1). In brief, attenuation-and scatter-corrected SPECT/CT images were acquired approximately 96 and 168 h after injection of 177 Lulilotomab satetraxetan.…”

“…177 Lu-lilotomab satetraxetan (previously referred to as 177 Lu-DOTA-HH1; trade name, Betalutin [Nordic Nanovector]) is a novel ARC that targets the CD37 antigen expressed on malignant B cells (1). Myelosuppression is the main adverse effect of the CD20-based ARC therapies 131 I-tositumomab (Bexxar; GlaxoSmithKline) and 90 Y-ibritumomabtiuxetan (Zevalin; Spectrum Pharmaceuticals) and is widely regarded to be a consequence of marrow irradiation (2,3).…”

The therapeutic effectiveness of 177Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2/M cell cycle arrest

“…Therefore, a conjugate that targets a different antigen could be desirable. Lutetium-177 [ 177 Lu]-lilotomab satetraxetan (Betalutin ® , previously known as 177 Lu-DOTA-HH1) is a next generation radioimmunoconjugate in which the murine mAb lilotomab targets CD37 receptors expressed on mature and malignant B cells [16,17], but also, at lower levels, in T cells, macrophages/monocytes, granulocytes, and dendritic cells [18]. 177 Lu is a beta-emitter with a mean beta energy of 0.133 MeV (mean and max beta-range in water: 0.23 and 1.9 mm).…”