Department of Diagnostic Physics, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
Department of Life Sciences and Health, Oslo Metropolitan University, Oslo, Norway.
Eur J Nucl Med Mol Imaging. 2018 Jul;45(7):1233-1241. doi: 10.1007/s00259-018-3964-9. Epub 2018 Feb 22.
Lu-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-in-human 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.
Two of the phase 1 arms included cold lilotomab pre-dosing (arm 1 and 4; 40 mg fixed and 100 mg/m 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 Lu-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.
Organs with distinct uptake of Lu-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 uptake was 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 2.67 mGy/MBq for arms 1-4, 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 = 0.05 and p = 0.02). No statistically significant difference between arms 1 and 4 was found.
RM is the primary dose-limiting organ for Lu-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/m 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.
Lu-lilotomab satetraxetan 是一种新型抗 CD37 抗体放射性核素偶联物，用于治疗非霍奇金淋巴瘤（NHL）。在一项复发 CD37+惰性 NHL 的首次人体 1/2a 期研究中，已经研究了四种不同组合的预给药和预处理的臂。本研究的目的是确定所有四个臂的肿瘤和正常组织吸收剂量，并研究肿瘤与风险器官吸收剂量比的可能变化。
两个 1 期臂包括冷 lilotomab 预给药（臂 1 和 4；分别为 40mg 固定剂量和 100mg/mBSA 剂量），两个臂不进行预给药（臂 2 和 3）。所有患者均接受不同方案的利妥昔单抗预处理。患者接受 10、15 或 20MBq/kg 体重的 Lu-lilotomab satetraxetan。19 名患者接受了剂量测定，共包括 47 个病变。吸收剂量是从多个 SPECT/CT 图像计算出来的，并根据每个患者的给药活度进行归一化。所有统计分析均采用双侧学生 t 检验。
除肿瘤外，骨髓（RM）、肝脏、脾脏和肾脏等器官也有明显的 Lu-lilotomab satetraxetan 摄取。对于臂 1-4，RM 的平均吸收剂量分别为 0.94、1.55、1.44 和 0.89mGy/MBq。对于未用 lilotomab 预给药的患者（臂 2 和 3 合并），RM 的平均吸收剂量为 1.48mGy/MBq，显著高于臂 1（p=0.04）和臂 4（p=0.02）。在其他器官中，脾脏的摄取量最高，而臂 4 患者的脾脏吸收剂量明显低于未进行 lilotomab 预给药的患者组（1.13 与 3.20mGy/MBq；p<0.01）。臂 1-4 的平均肿瘤吸收剂量分别为 2.15、2.31、1.33 和 2.67mGy/MBq。对每位患者的肿瘤吸收剂量进行平均后，得到患者平均肿瘤吸收剂量与 RM 吸收剂量比值，对于未进行 lilotomab 预给药的患者组，平均值为 1.07，对于臂 1 为 2.16，对于臂 4 为 4.62。与未预给药组相比，臂 1 和臂 4 的比值均显著升高（p=0.05 和 p=0.02）。臂 1 和臂 4 之间未发现统计学差异。
RM 是 Lu-lilotomab satetraxetan 治疗的主要剂量限制器官，而 lilotomab 预给药具有减轻 RM 吸收剂量的作用。将 lilotomab 的剂量从 40mg 增加到 100mg/m 发现 RM 吸收剂量略有降低，肿瘤与 RM 吸收剂量的比值增加。尽管如此，两种预剂量都导致肿瘤与 RM 吸收剂量的比值显著增加。这些发现鼓励继续使用 lilotomab 预给药。
