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. 2005 Jan;19(1):118-25. doi: 10.1038/sj.leu.2403575.


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, beta-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/m(2)). 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 x 10(6)/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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / pharmacokinetics
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Melphalan / administration & dosage
  • Melphalan / pharmacokinetics
  • Melphalan / therapeutic use*
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / radiotherapy*
  • Multiple Myeloma / surgery*
  • Organometallic Compounds / administration & dosage*
  • Organophosphorus Compounds / administration & dosage*
  • Radioisotopes / administration & dosage*
  • Samarium
  • Stem Cell Transplantation*
  • Tissue Distribution
  • Transplantation Conditioning*


  • Antineoplastic Agents, Alkylating
  • Organometallic Compounds
  • Organophosphorus Compounds
  • Radioisotopes
  • Samarium
  • samarium Sm-153 lexidronam
  • Melphalan