A Phase II study of (153)Sm-EDTMP and high-dose melphalan as a peripheral blood stem cell conditioning regimen in patients with multiple myeloma.

Abstract

Multiple myeloma (MM) remains an incurable illness affecting nearly 20,000 individuals in the United States per year. High-dose melphalan (HDM) with autologous hematopoietic stem cell support (ASCT) is one of the mainstays of therapy for younger patients, but little advancement has been made with regards to conditioning regimens. We opted to combine (153)Samarium ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP), a radiopharmaceutical approved for the palliation of pain caused by metastatic bone lesions, with HDM and ASCT in a Phase II study. Individualized doses of (153)Sm were based on dosimetry and were calculated to deliver 40 Gy to the bone marrow. The therapeutic dose of (153)Sm-EDTMP was followed by HDM and ASCT. Forty-six patients with newly diagnosed or relapsed disease were treated. Study patients were compared to 102 patients contemporaneously treated with HDM and ASCT. Fifty-nine percent of study patients achieved a very good partial response (VGPR) or better. With a median follow-up of 7.1 years, the median overall survival and progression free survival (PFS) from study registration was 6.2 years (95% CI 4.6-7.5 years) and 1.5 years (1.1-2.2 years), respectively, which compared favorably to contemporaneously treated non-study patients. Addition of high-dose (153)Sm-EDTMP to melphalan conditioning appears to be safe, well tolerated, and worthy of further study in the context of novel agents and in the Phase III setting.

• Authors: Angela Dispenzieri, Gregory A Wiseman, Martha Q Lacy, Suzanne R Hayman, Shaji K Kumar, Francis Buadi, David Dingli, Krista M Laumann, Jake Allred, Susan M Geyer, Mark R Litzow, Dennis A Gastineau, David J Inwards, Ivana N Micallef, Stephen M Ansell, Luis Porrata, Michelle A Elliott, Patrick B Johnston, William J Hogan, Morie A Gertz
• Journal: American journal of hematology (Am J Hematol) Vol. 85 Issue 6 Pg. 409-13 (Jun 2010) ISSN: 1096-8652 [Electronic] United States
• PMID: 20513117 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Wiley-Liss, Inc.

Chemical References

• Myeloablative Agonists
• Organometallic Compounds
• Organophosphorus Compounds
• Radioisotopes
• Radiopharmaceuticals
• Samarium
• samarium Sm-153 lexidronam
• Melphalan

Topics

• Adult
• Aged
• Bone Marrow (drug effects, radiation effects)
• Disease-Free Survival
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Melphalan (administration & dosage, pharmacology, therapeutic use)
• Middle Aged
• Multiple Myeloma (blood, drug therapy, surgery)
• Myeloablative Agonists (administration & dosage, pharmacology, therapeutic use)
• Organometallic Compounds (administration & dosage, pharmacokinetics, therapeutic use)
• Organophosphorus Compounds (administration & dosage, pharmacokinetics, therapeutic use)
• Pain (radiotherapy)
• Peripheral Blood Stem Cell Transplantation
• Radioisotopes (administration & dosage, pharmacokinetics, therapeutic use)
• Radiopharmaceuticals (administration & dosage, pharmacokinetics, therapeutic use)
• Radiotherapy Dosage
• Salvage Therapy
• Samarium (administration & dosage, pharmacokinetics, therapeutic use)
• Tissue Distribution
• Transplantation Conditioning (methods)