Phase I trial of systemic administration of Edmonston strain of measles virus genetically engineered to express the sodium iodide symporter in patients with recurrent or refractory multiple myeloma.
Phase I trial of systemic administration of Edmonston strain of measles virus genetically engineered to express the sodium iodide symporter in patients with recurrent or refractory multiple myeloma.
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DOI：
10.1038/leu.2017.120
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发表时间：
2017-12
期刊：
影响因子：
11.4
通讯作者：
Russell SJ
中科院分区：
文献类型：
--
作者：
Dispenzieri A;Tong C;LaPlant B;Lacy MQ;Laumann K;Dingli D;Zhou Y;Federspiel MJ;Gertz MA;Hayman S;Buadi F;O'Connor M;Lowe VJ;Peng KW;Russell SJ
MV-NIS是一种表达人钠碘同向转运体的埃德蒙顿系溶瘤麻疹病毒--一种通过放射性碘非侵入性成像进行监测的手段。已探索所有其他治疗方案的复发性、难治性骨髓瘤患者有资格参加本I期试验。队列1接受静脉MV-NIS治疗，队列2在MV-NIS前2天接受环磷酰胺治疗。32名患者接受了治疗。队列1最初入组4个剂量水平，但未达到MTD，随后当改进的病毒生产技术使其成为可能时，入组2个更高的剂量水平。队列1未达到MTD，TCID 50 1011是MV-NIS单药II期试验中使用的剂量。所有剂量水平下两个队列中的3-4级AE为：中性粒细胞减少症（n=9）;白细胞计数降低（n=5）;血小板减少症（n=2）;以及CD 4淋巴细胞减少、贫血和淋巴细胞减少症（各n=1）。从漱口液、血液和尿液中扩增MV-N RNA序列。123 I显像阳性8例。1例患者达到CR;在其他患者中观察到血清FLC一过性下降。MV-NIS能够在被免疫系统清除之前复制。溶瘤病毒为靶向感染和破坏播散性骨髓瘤提供了一种有前途的新模式。
MV-NIS is an Edmonston-lineage oncolytic measles virus expressing the human sodium-iodide symporter--a means for monitoring by noninvasive imaging of radioiodine. Patients with relapsed, refractory myeloma who had explored all other treatment options were eligible for this Phase I trial. Cohort 1 was treated with intravenous MV-NIS, and Cohort 2 received cyclophosphamide two days prior to MV-NIS. Thirty-two patients were treated. Cohort 1 initially enrolled to 4 dose-levels without reaching MTD and subsequently to 2 higher dose-levels when improved virus manufacture technology made it possible. MTD was not reached in Cohort 1, and TCID50 1011 is the dose being used in a Phase II trial of single agent MV-NIS. Grade 3–4 AEs in both cohorts at all dose levels were: neutropenia (n=9); leukocyte count decreased (n=5); thrombocytopenia (n=2); and CD4 lymphocytes decreased, anemia and lymphopenia (each n=1). MV-N RNA sequences were amplified from gargle specimens, blood and urine. 123I scans were positive in 8 patients. One patient achieved a CR; transient drops in serum FLCs were seen in other patients. MV-NIS is capable of replicating before being cleared by the immune system. Oncolytic viruses offer a promising new modality for the targeted infection and destruction of disseminated myeloma.
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影响因子：
11.2
作者：
Galanis E;Atherton PJ;Maurer MJ;Knutson KL;Dowdy SC;Cliby WA;Haluska P Jr;Long HJ;Oberg A;Aderca I;Block MS;Bakkum-Gamez J;Federspiel MJ;Russell SJ;Kalli KR;Keeney G;Peng KW;Hartmann LC
通讯作者：
Hartmann LC
影响因子：
2.7
作者：
Nielsen, L;Blixenkrone-Moller, M;Bolt, G
通讯作者：
Bolt, G
影响因子：
2.6
作者：
Ong, Hooi Tin;Timm, Michael M.;Peng, Kah-Whye
通讯作者：
Peng, Kah-Whye
影响因子：
11.4
作者：
Durie, B. G. M.;Harousseau, J-L;Rajkumar, S. V.
通讯作者：
Rajkumar, S. V.
影响因子：
3.6
作者：
Jurianz, K;Ziegler, S;Kirschfink, M
通讯作者：
Kirschfink, M