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Myeloma

A phase I study of 153Sm-EDTMP with fixed high-dose melphalan as a peripheral blood stem cell conditioning regimen in patients with multiple myeloma

Leukemia volume 19, pages 118–125 (2005)Cite this article

Abstract

Despite response rates of 30% after high-dose chemotherapy with autologous hematopoietic stem cell transplant, patients with multiple myeloma are not cured. 153Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP; Quadramet®) is a short-range, β-emitting therapeutic radiopharmaceutical with avid skeletal uptake. In total, 12 patients were treated with escalating doses of 153Sm-EDTMP (N=3/group; 6, 12, 19.8, and 30 mCi/kg) and a fixed dose of melphalan (200 mg/m2). No dose limiting toxicity was seen. To better standardize the marrow compartment radiation dose, the study was modified such that an additional six patients were treated at a targeted absorbed radiation dose to the red marrow of 40 Gy based on a trace labeled infusion 1 week prior to the therapy. Despite rapid elimination of unbound radiopharmaceutical via kidneys and bladder, no episodes of nephrotoxicity, hemorrhagic cystitis, or delayed radiation nephritis were observed with a median follow-up of 31 months (range 8.5–44). Median times to ANC>0.5 and platelet >20 × 106/l were 12 and 11 days, respectively, with no graft failures. Overall response rate was 94% including seven very good partial responses and five complete responses. Addition of 153Sm EDTMP to melphalan conditioning appears to be safe, well-tolerated and worthy of further study.

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Acknowledgements

We thank the nursing staff, physician extenders, and allied health staff in the GCRC and Transplant Center. Margo Marzloff is acknowledged for her work as this study's clinical research assistant, William L Dunn for nuclear medicine dosimetry and biodistribution calculations, and Pamela Atherton for her assistance in data analysis. Finally, Dr Brian Mullan and co-workers in Nuclear Medicine at Mayo have been invaluable for their encouragement in the development, testing, and dissemination of information concerning innovative new therapies for our patients. This trial was supported in part by grant M01-RR00585, CA 15083 and the Mayo Clinic Hematology Malignancies Fund.

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Authors and Affiliations

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

    A Dispenzieri, M Q Lacy, M R Litzow, P M Anderson, D A Gastineau, A Tefferi, D J Inwards, I N M Micallef, S M Ansell, L Porrata, M A Elliott, J A Lust, P R Greipp, S V Rajkumar, T E Witzig & M A Gertz

  2. Department of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, Rochester, MN, USA

    A Dispenzieri & J A Lust

  3. Department of Radiology (Nuclear Medicine), Mayo Clinic, Rochester, MN, USA

    G A Wiseman

  4. Department of Pediatrics, Division of Hematology/Oncology, Mayo Clinic, Rochester, MN, USA

    P M Anderson

  5. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA

    D A Gastineau

  6. Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, MN, USA

    P R Greipp, S V Rajkumar & T E Witzig

  7. Department of Internal Medicine, Division of Hematology, Mayo Clinic, Scottsdale, AZ, USA

    R Fonseca

  8. Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA

    C Erlichman

  9. Department of Biostatistics, Mayo Clinic, Rochester, MN, USA

    J A Sloan

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Correspondence to A Dispenzieri.

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Dispenzieri, A., Wiseman, G., Lacy, M. et al. A phase I study of 153Sm-EDTMP with fixed high-dose melphalan as a peripheral blood stem cell conditioning regimen in patients with multiple myeloma. Leukemia 19, 118–125 (2005). https://doi.org/10.1038/sj.leu.2403575

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