Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Mol Imaging Biol. 2022 Oct;24(5):807-817. doi: 10.1007/s11307-022-01731-3. Epub 2022 Apr 29.
[Lu]Lu-lilotomab satetraxetan, a novel CD37 directed radioimmunotherapy (RIT), has been investigated in a first-in-human phase 1/2a study for relapsed indolent non-Hodgkin lymphoma. In this study, new methods were assessed to calculate the mean absorbed dose to the total tumor volume, with the aim of establishing potential dose-response relationships based on 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) parameters and clinical response. Our second aim was to study if higher total tumor burden induces reduction in the Lu-lilotomab satetraxetan accumulation in tumor.
Fifteen patients with different pre-dosing (non-radioactive lilotomab) regimens were included and the cohort was divided into low and high non-radioactive lilotomab pre-dosing groups for some of the analyses. Lu-lilotomab satetraxetan was administered at dosage levels of 10, 15, or 20 MBq/kg. Mean absorbed doses to the total tumor volume (tTAD) were calculated from posttreatment single-photon emission tomography (SPECT)/computed tomography (CT) acquisitions. Total values of metabolic tumor volume (tMTV), total lesion glycolysis (tTLG) and the percent change in these parameters were calculated from FDG PET/CT performed at baseline, and at 3 and 6 months after RIT. Clinical responses were evaluated at 6 months as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).
Significant decreases in tMTV and tTLG were observed at 3 months for patients receiving tTAD ≥ 200 cGy compared to patients receiving tTAD < 200 cGy (p = .03 for both). All non-responders had tTAD < 200 cGy. Large variations in tTAD were observed in responders. Reduction in Lu-lilotomab satetraxetan uptake in tumor volume was not observed in patients with higher baseline tumor burden (tTMV).
tTAD of ≥ 200 cGy may prove valuable to ensure clinical response, but further studies are needed to confirm this in a larger patient population. Furthermore, this work indicates that higher baseline tumor burden (up to 585 cm) did not induce reduction in radioimmunoconjugate accumulation in tumor.
[Lu]Lu-卢利洛单抗 satetraxetan，一种新型的 CD37 导向的放射免疫疗法（RIT），已在复发惰性非霍奇金淋巴瘤的首次人体 1/2a 期研究中进行了研究。在这项研究中，评估了新的方法来计算总肿瘤体积的平均吸收剂量，目的是基于 2-脱氧-2-[18F]氟-D-葡萄糖（FDG）正电子发射断层扫描（PET）参数和临床反应建立潜在的剂量反应关系。我们的第二个目的是研究更高的总肿瘤负担是否会导致肿瘤中 Lu-lilotomab satetraxetan 积累的减少。
纳入了 15 名接受不同预给药（非放射性 lilotomab）方案的患者，并根据一些分析将队列分为低和高非放射性 lilotomab 预给药组。以 10、15 或 20 MBq/kg 的剂量水平给予 Lu-lilotomab satetraxetan。从治疗后单光子发射断层扫描（SPECT）/计算机断层扫描（CT）采集计算总肿瘤体积（tTAD）的平均吸收剂量。基线时进行 FDG PET/CT 检查，计算代谢肿瘤体积（tMTV）、总病变糖酵解（tTLG）和这些参数的百分比变化值，并在 RIT 后 3 个月和 6 个月进行。6 个月时根据完全缓解（CR）、部分缓解（PR）、稳定疾病（SD）或进展性疾病（PD）评估临床反应。
与接受 tTAD <200 cGy 的患者相比，接受 tTAD ≥200 cGy 的患者在 3 个月时 tMTV 和 tTLG 显著下降（两者均为 p=0.03）。所有无反应者的 tTAD <200 cGy。 responders 中观察到 tTAD 变化较大。在基线肿瘤负担较高的患者中（tTMV）未观察到肿瘤体积中 Lu-lilotomab satetraxetan 摄取的减少。
tTAD ≥200 cGy 可能有助于确保临床反应，但需要进一步的研究来证实这一点。此外，这项工作表明，更高的基线肿瘤负担（高达 585 cm）并没有导致放射性免疫偶联物在肿瘤中的积累减少。
