From the Department of Nuclear Medicine.
Division of Hematology and Oncology, Department of Internal Medicine II, University Hospital Würzburg, Würzburg.
Clin Nucl Med. 2024 Feb 1;49(2):146-151. doi: 10.1097/RLU.0000000000004974. Epub 2023 Nov 29.
After C-X-C motif chemokine receptor 4 (CXCR4)-directed radioligand therapy (RLT), lymphoma patients are scheduled for conditioning therapy (CON) followed by hematopoietic stem cell transplantation (HSCT). We aimed to determine whether CXCR4-RLT can achieve bone marrow ablation and direct antilymphoma activity independent from CON/HSCT and also evaluated the safety profile of this theranostic approach in an acute setting.
After CXCR4-directed 68 Ga-pentixafor PET/CT, 21 heavily pretreated patients with hematological malignancies underwent CXCR4-directed RLT using 90 Y-pentixather. The extent of myeloablative efficacy was determined by investigating hematologic laboratory parameters before RLT (day -1), at the day of RLT (day 0), 2 days after RLT (day 2), and before CON (median day 10). Serving as surrogate marker of antilymphoma activity, lactate dehydrogenase (LDH) levels were also assessed until CON. We also screened for laboratory-defined tumor lysis syndrome after the Cairo-Bishop definition and recorded acute laboratory adverse events using the Common Terminology Criteria for Adverse Events version 5.0.
After RLT, we observed a significant decline of leukocyte levels by 79.4% ± 18.7% till CON (granulocytes, drop by 70.3% ± 21%; platelets, reduction by 43.1% ± 36%; P ≤ 0.0005 vs day 0, respectively). After RLT, LDH levels already reached a peak at day 2, which was followed by a rapid decline thereafter (peak vs day of CON, P = 0.0006), indicating that 90 Y-pentixather exhibits direct antilymphoma activity. At day of CON, LDH levels were also significantly lower when compared with day -1 ( P = 0.04), suggestive for durable response mediated by RLT. No patient fulfilled the criteria of tumor lysis syndrome, whereas 25 laboratory adverse events attributable to CXCR4-directed treatment were identified (≥grade 3 in 2/25 [8%]). During further treatment course, all patients (100%) received HSCT.
CXCR4-directed RLT causes effective myeloablation, which allows for HSCT. In addition, it also exerts direct antilymphoma activity independent of subsequent therapeutic steps, whereas safety profile was acceptable.
在 C-X-C 基序趋化因子受体 4（CXCR4）导向的放射性配体治疗（RLT）后，淋巴瘤患者计划接受预处理（CON），然后进行造血干细胞移植（HSCT）。我们旨在确定 CXCR4-RLT 是否可以在不依赖 CON/HSCT 的情况下实现骨髓消融和直接抗淋巴瘤活性，并在急性环境中评估这种治疗方法的安全性。
在 CXCR4 导向的 68 Ga-戊替卡肽 PET/CT 后，21 名患有血液系统恶性肿瘤的预处理过的患者接受了 90 Y-戊替卡肽的 CXCR4 导向的 RLT。通过在 RLT 前（第-1 天）、RLT 当天（第 0 天）、RLT 后 2 天（第 2 天）和 CON 前（中位数第 10 天）检测血液学实验室参数来确定骨髓消融的程度。作为抗淋巴瘤活性的替代标志物，乳酸脱氢酶（LDH）水平也在 CON 之前进行评估。我们还根据开罗-比什科普定义筛查了实验室定义的肿瘤溶解综合征，并使用通用不良事件术语标准 5.0 记录了急性实验室不良事件。
RLT 后，白细胞水平显著下降，直至 CON 下降 79.4%±18.7%（粒细胞下降 70.3%±21%；血小板下降 43.1%±36%；分别为 P≤0.0005 与第 0 天）。RLT 后，LDH 水平在第 2 天达到峰值，此后迅速下降（与 CON 日相比，P=0.0006），表明 90 Y-戊替卡肽具有直接抗淋巴瘤活性。在 CON 日，与第-1 天相比，LDH 水平也显著降低（P=0.04），提示 RLT 介导的持久反应。没有患者符合肿瘤溶解综合征的标准，而 25 项归因于 CXCR4 定向治疗的实验室不良事件被确定（≥3 级的 25/25 [8%]）。在进一步的治疗过程中，所有患者（100%）均接受了 HSCT。
CXCR4 导向的 RLT 可引起有效的骨髓消融，从而允许进行 HSCT。此外，它还在不依赖后续治疗步骤的情况下发挥直接的抗淋巴瘤活性，且安全性可接受。
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