Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
Bone Marrow Transplant. 2017 Oct;52(10):1372-1377. doi: 10.1038/bmt.2017.164. Epub 2017 Sep 4.
This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan (Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m with indium-111 ibritumomab tiuxetan (In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m with escalating doses of Y-Zevalin (day -14); melphalan 100 mg/m (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment. Each patient's In-Zevalin dosimetry data were used to calculate the dose of Y-Zevalin (in mCi) to deliver 10, 12, 14, 16, 18 or 20 Gy to the liver. Dose limiting toxicities were seen in 3 patients. The overall response rate was 73% (22/30) with stringent complete response in 2 patients; complete response, 5; very good partial response, 12; and partial response, 3. The median PFS was 16.5 months and the median overall survival was 63.4 months. In MM, the MTD of Y-Zevalin with HDM is 18 Gy to the liver. The addition of radiation with novel delivery methods such as radioimmunotherapy combined with standard transplant regimens warrants further study.
这项 1 期研究（临床试验 NCT00477815）旨在确定多发性骨髓瘤（MM）患者在接受自体干细胞移植（ASCT）前接受高剂量马法兰（HDM）治疗时，钇-90 依替曲昔单抗（Y-Zevalin）的最大耐受剂量（MTD）。在 3+3 试验设计中，30 名患者在第 -22 天接受利妥昔单抗 250mg/m2 联合铟-111 依替曲昔单抗（In-Zevalin）进行剂量测定；在第 -14 天接受利妥昔单抗 250mg/m2 联合递增剂量的 Y-Zevalin；在第 -2、-1 天接受马法兰 100mg/m2，随后在第 0 天进行 ASCT 和沙格司亭（GM-CSF，第 0 天），直至中性粒细胞植入。每位患者的 In-Zevalin 剂量测定数据用于计算 Y-Zevalin（mCi）的剂量，以向肝脏输送 10、12、14、16、18 或 20Gy。3 名患者出现剂量限制性毒性。总缓解率为 73%（22/30），2 名患者达到严格完全缓解；完全缓解 5 例；非常好的部分缓解 12 例；部分缓解 3 例。中位无进展生存期为 16.5 个月，中位总生存期为 63.4 个月。在 MM 中，Y-Zevalin 联合 HDM 的 MTD 为向肝脏输送 18Gy。需要进一步研究与标准移植方案联合的新型给药方法（如放射性免疫治疗）联合放射治疗的疗效。
