A phase 1 trial of 90Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma

A. Dispenzieri; A. D'Souza; M. A. Gertz; K. Laumann; G. Wiseman; M. Q. Lacy; B. LaPlant; F. Buadi; S. R. Hayman; S. K. Kumar; D. Dingli; W. J. Hogan; S. M. Ansell; D. A. Gastineau; D. J. Inwards; I. N. Micallef; L. F. Porrata; P. B. Johnston; M. R. Litzow; T. E. Witzig

doi:10.1038/bmt.2017.164

A phase 1 trial of ⁹⁰Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma

A. Dispenzieri, A. D'Souza, M. A. Gertz, K. Laumann, G. Wiseman, M. Q. Lacy, B. LaPlant, F. Buadi, S. R. Hayman, S. K. Kumar, D. Dingli, W. J. Hogan, S. M. Ansell, D. A. Gastineau, D. J. Inwards, I. N. Micallef, L. F. Porrata, P. B. Johnston, M. R. Litzow, T. E. Witzig

Hematology

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan (⁹⁰Y-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/m² with indium-111 ibritumomab tiuxetan (¹¹¹In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m² with escalating doses of ⁹⁰Y-Zevalin (day -14); melphalan 100 mg/m² (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment. Each patient's ¹¹¹In-Zevalin dosimetry data were used to calculate the dose of ⁹⁰Y-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 ⁹⁰Y-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.

Original language	English (US)
Pages (from-to)	1372-1377
Number of pages	6
Journal	Bone Marrow Transplantation
Volume	52
Issue number	10
DOIs	https://doi.org/10.1038/bmt.2017.164
State	Published - Oct 1 2017

ASJC Scopus subject areas

Hematology
Transplantation

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Dispenzieri, A., D'Souza, A., Gertz, M. A., Laumann, K., Wiseman, G., Lacy, M. Q., LaPlant, B., Buadi, F., Hayman, S. R., Kumar, S. K., Dingli, D., Hogan, W. J., Ansell, S. M., Gastineau, D. A., Inwards, D. J., Micallef, I. N., Porrata, L. F., Johnston, P. B., Litzow, M. R., & Witzig, T. E. (2017). A phase 1 trial of ⁹⁰Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma. Bone Marrow Transplantation, 52(10), 1372-1377. https://doi.org/10.1038/bmt.2017.164

Dispenzieri, A, D'Souza, A, Gertz, MA, Laumann, K, Wiseman, G, Lacy, MQ, LaPlant, B, Buadi, F, Hayman, SR, Kumar, SK , Dingli, D , Hogan, WJ , Ansell, SM, Gastineau, DA, Inwards, DJ, Micallef, IN, Porrata, LF, Johnston, PB , Litzow, MR & Witzig, TE 2017, 'A phase 1 trial of ⁹⁰Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma', Bone Marrow Transplantation, vol. 52, no. 10, pp. 1372-1377. https://doi.org/10.1038/bmt.2017.164

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title = "A phase 1 trial of 90Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma",

abstract = "This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan (90Y-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/m2 with indium-111 ibritumomab tiuxetan (111In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m2 with escalating doses of 90Y-Zevalin (day -14); melphalan 100 mg/m2 (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment. Each patient's 111In-Zevalin dosimetry data were used to calculate the dose of 90Y-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 90Y-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.",

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AU - Laumann, K.

AU - Wiseman, G.

AU - Lacy, M. Q.

AU - LaPlant, B.

AU - Buadi, F.

AU - Hayman, S. R.

AU - Kumar, S. K.

AU - Dingli, D.

AU - Hogan, W. J.

AU - Ansell, S. M.

AU - Gastineau, D. A.

AU - Inwards, D. J.

AU - Micallef, I. N.

AU - Porrata, L. F.

AU - Johnston, P. B.

AU - Litzow, M. R.

AU - Witzig, T. E.

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A phase 1 trial of ⁹⁰Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma

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