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

Angela Dispenzieri, C. Tong, B. LaPlant, Martha Lacy, K. Laumann, David M Dingli, Y. Zhou, Mark J Federspiel, Morie Gertz, S. Hayman, F. Buadi, M. O'Connor, Val Lowe, Kah-Whye Peng, Stephen J Russell

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27 Citations (Scopus)

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.Leukemia advance online publication, 19 May 2017; doi:10.1038/leu.2017.120.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - Apr 25 2017

Fingerprint

Measles virus
Multiple Myeloma
Oncolytic Viruses
Maximum Tolerated Dose
Sodium Iodide
Lymphopenia
Neutropenia
Leukocyte Count
Cyclophosphamide
Publications
Anemia
Immune System
Leukemia
sodium-iodide symporter
Urine
Lymphocytes
Viruses
Technology
Light
Infection

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

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title = "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",
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.Leukemia advance online publication, 19 May 2017; doi:10.1038/leu.2017.120.",
author = "Angela Dispenzieri and C. Tong and B. LaPlant and Martha Lacy and K. Laumann and Dingli, {David M} and Y. Zhou and Federspiel, {Mark J} and Morie Gertz and S. Hayman and F. Buadi and M. O'Connor and Val Lowe and Kah-Whye Peng and Russell, {Stephen J}",
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T1 - 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

AU - Dispenzieri, Angela

AU - Tong, C.

AU - LaPlant, B.

AU - Lacy, Martha

AU - Laumann, K.

AU - Dingli, David M

AU - Zhou, Y.

AU - Federspiel, Mark J

AU - Gertz, Morie

AU - Hayman, S.

AU - Buadi, F.

AU - O'Connor, M.

AU - Lowe, Val

AU - Peng, Kah-Whye

AU - Russell, Stephen J

PY - 2017/4/25

Y1 - 2017/4/25

N2 - 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.Leukemia advance online publication, 19 May 2017; doi:10.1038/leu.2017.120.

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