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Early phase studies

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

Leukemia volume 31, pages 2791–2798 (2017)Cite this article

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Abstract

MV-NIS is an Edmonston lineage oncolytic measles virus expressing the human sodium iodide symporter—a means for monitoring by non-invasive 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 2 days prior to MV-NIS. Thirty-two patients were treated. Cohort 1 initially enrolled to four dose levels without reaching maximum tolerated dose (MTD) and subsequently to two 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 adverse events 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 eight patients. One patient achieved a complete response; transient drops in serum free light chains 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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Acknowledgements

This work was supported by funds from the NIH/NCI (R01CA125614, R01CA168719, UL1 TR000135), Al and Mary Agnes McQuinn, the Siebens Foundation, the Richard M Schulze Family Foundation. The NCI (RAID Program) supported cGMP virus manufacture and toxicology/pharmacology studies.

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Authors and Affiliations

  1. Department of Hematology, Mayo Clinic, Rochester, MN, USA

    A Dispenzieri, C Tong, B LaPlant, M Q Lacy, K Laumann, D Dingli, Y Zhou, M J Federspiel, M A Gertz, S Hayman, F Buadi, M O'Connor, V J Lowe, K-W Peng & S J Russell

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  1. A Dispenzieri
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Correspondence to A Dispenzieri.

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Competing interests

SJR Co-founder, CEO and Board Member of Vyriad. K-WP Co-founder and CTO of Vyriad (Chief Technical Officer). MJF Co-founder of Vyriad. All three also hold equity in Vyriad. The remaining authors declare no conflict of interest.

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Dispenzieri, A., Tong, C., LaPlant, B. et al. 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. Leukemia 31, 2791–2798 (2017). https://doi.org/10.1038/leu.2017.120

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