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Plasma Cell Disorders

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

Bone Marrow Transplantation volume 52, pages 1372–1377 (2017)Cite this article

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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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Acknowledgements

We thank the RN transplant coordinators—Teresa Miceli, Joan Theuer, Marsha Knudsvig, Michelle Gronseth and Lisa Kaiser for their assistance in patient accrual. We are extremely grateful for the philanthropic support provided by a gift from Hank Asher, which was paramount in our work to advance the treatment of multiple myeloma—an ongoing focus of investigation at Mayo Clinic for over 40 years.

Author contributions

AD, ADS and TEW contributed to the study design, data analysis and collection, care of patients, writing and edited the manuscript. KL contributed to data analysis and collection and the writing and editing of the manuscript. GW assisted with study design, data collection, care of patients and manuscript editing. BL contributed to the study design, data analysis and collection and manuscript editing. MQL, FB, SRH, SKK, DD, WJH, SMA, DAG, DJI, INM, LFP, PBJ, MRL all contributed to data collection, care of patients and editing of the manuscript. MAG provided care of patients and manuscript editing.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    A Dispenzieri, M A Gertz, M Q Lacy, 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

  2. Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    A D'Souza

  3. Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

    K Laumann & B LaPlant

  4. Division of Nuclear Medicine, Mayo Clinic, Rochester, MN, USA

    G Wiseman

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  1. A Dispenzieri
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Correspondence to A Dispenzieri or T E Witzig.

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The authors declare no conflict of interest.

Additional information

This work was presented at the 2011 ASH Annual Meeting, San Diego, CA, USA. Blood (ASH Annual Meeting Abstracts) 2011; 118: Abstract 3095. This trial is registered at https://clinicaltrials.gov as NCT00477815.

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Dispenzieri, A., D'Souza, A., Gertz, M. et al. A phase 1 trial of 90Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma. Bone Marrow Transplant 52, 1372–1377 (2017). https://doi.org/10.1038/bmt.2017.164

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