Dreher Niklas, Dörrler Anna-Lena, Kraus Sabrina, Rasche Leo, Higuchi Takahiro, Samnick Samuel, Lapa Constantin, Einsele Hermann, Serfling Sebastian E, Buck Andreas K, Werner Rudolf A
Department of Nuclear Medicine, University Hospital Würzburg, Würzburg.
Nuclear Medicine, Faculty of Medicine, University of Augsburg, Augsburg.
Clin Nucl Med. 2025 Jun 1;50(6):495-500. doi: 10.1097/RLU.0000000000005813. Epub 2025 Mar 5.
Markedly expressed on hematopoietic stem cells, C-X-C motif chemokine receptor 4 (CXCR4)-directed radioligand therapy (RLT) has been used in relapsed/refractory (r/r) MM to prepare for hematopoietic stem cell transplantation (HSCT). We aimed to determine the myeloablative efficacy of CXCR4 RLT in MM patients and assessed the safety profile of this treatment.
Thirty-eight patients with r/r MM were treated with 40 cycles of CXCR4-targeting [ 90 Y]Y-PentixaTher or [ 177 Lu]Lu-PentixaTher. Myeloablative dynamics were closely monitored by examining hematologic parameters before the application of RLT (day 1), on day 2, and on the start day of conditioning chemotherapy (CON, median day 10). Laboratory parameters evaluating organ toxicity were collected and categorized following the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Cairo-Bishop classification was also applied to identify patients experiencing laboratory tumor lysis syndrome (TLS) caused by RLT. After CON, we determined the rate of patients receiving hematopoietic stem cell transplantation (HSCT) followed by successful neutrophile engraftment.
Forty cycles of CXCR4-directed RLT were applied. Myeloablative effects resulted in an 81.8% decline in leukocytes and a 69.4% decrease in neutrophil levels till the day of CON ( P <0.0001, respectively), followed by platelets (63.1%; P <0.0001) and hemoglobin (9%; P =0.002). We observed 58 AE Events (1/58 [1.7%], ≥ grade 3). CON could be applied successfully after 39/40 (97.5%) cycles. After CON, in 39/39 (100%) of the cycles, HSCT was conducted, and successful neutrophil engraftment was reached after 37/39 (94.9%) of these cycles.
CXCR4-directed RLT exerted relevant myeloablative effects. When performing HSCT after applying additional CON, successful neutrophile engraftment was reached in the vast majority of the cases.
C-X-C基序趋化因子受体4（CXCR4）导向的放射性配体疗法（RLT）在造血干细胞上显著表达，已用于复发/难治性（r/r）多发性骨髓瘤（MM）患者，为造血干细胞移植（HSCT）做准备。我们旨在确定CXCR4 RLT对MM患者的清髓效果，并评估该治疗的安全性。
38例r/r MM患者接受了40个周期的靶向CXCR4的[90Y]Y-喷替肽或[177Lu]Lu-喷替肽治疗。通过在RLT应用前（第1天）、第2天以及预处理化疗开始日（CON，中位第10天）检查血液学参数，密切监测清髓动态。按照不良事件通用术语标准（CTCAE）第5.0版收集并分类评估器官毒性的实验室参数。还应用开罗-毕晓普分类法来识别因RLT导致实验室肿瘤溶解综合征（TLS）的患者。在CON之后，我们确定接受造血干细胞移植（HSCT）并随后成功实现中性粒细胞植入的患者比例。
应用了40个周期的CXCR4导向的RLT。清髓效果导致直至CON日白细胞下降81.8%，中性粒细胞水平下降69.4%（P均<0.0001），随后血小板下降63.1%（P<0.0001），血红蛋白下降9%（P=0.002）。我们观察到58例不良事件（1/58[1.7%]，≥3级）。39/40（97.5%）个周期后可成功进行CON。在CON之后，39/39（100%）个周期进行了HSCT，其中37/39（94.9%）个周期成功实现了中性粒细胞植入。
CXCR4导向的RLT发挥了相关清髓作用。在应用额外的CON后进行HSCT时，绝大多数病例成功实现了中性粒细胞植入。
