Lapa Constantin, Herrmann Ken, Schirbel Andreas, Hänscheid Heribert, Lückerath Katharina, Schottelius Margret, Kircher Malte, Werner Rudolf A, Schreder Martin, Samnick Samuel, Kropf Saskia, Knop Stefan, Buck Andreas K, Einsele Hermann, Wester Hans-Juergen, Kortüm K Martin
Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Theranostics. 2017 Apr 8;7(6):1589-1597. doi: 10.7150/thno.19050. eCollection 2017.
C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM). Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival. ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive. CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.
C-X-C基序趋化因子受体4（CXCR4）是多种人类癌症中肿瘤生长和转移的关键因素。我们最近报道了在多发性骨髓瘤（MM）中使用CXCR4导向的内照射放疗（ERT）的首例人体试验取得了令人鼓舞的结果。8例经过多次预处理的MM患者共接受了10个ERT周期（7例患者接受1个周期，1例患者接受3个周期）。ERT与化疗和自体干细胞支持联合使用。观察终点为不良事件的发生情况和时间、无进展生存期和总生存期。ERT总体耐受性良好，未出现任何意外的急性不良事件或生命体征变化。对于髓内或髓外病变吸收肿瘤剂量>30-70 Gy的患者，观察到显著的抗骨髓瘤活性，1例患者达到完全缓解，5/8例患者部分缓解。ERT后不久，1例患者出现严重感染并发症，在ERT后22天死于败血症，另1例肿瘤负荷高的患者发生致命的肿瘤溶解综合征。中位无进展生存期为54天（范围13-175天），中位总生存期为223天（范围13-313天）。在随访期间（6例患者可供随访），1例患者死于感染并发症，2/8例患者死于疾病进展，其余3/8例患者仍存活。CXCR4导向的ERT耐受性良好，即使在伴有髓外疾病的非常晚期MM患者中也能发挥抗骨髓瘤活性。非常有必要对这种新的治疗选择进行进一步评估。
