166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials. Academic Article uri icon

Overview

abstract

  • Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation.

authors

  • Giralt, Sergio
  • Bensinger, William
  • Goodman, Mark
  • Podoloff, Donald
  • Eary, Janet
  • Wendt, Richard
  • Alexanian, Raymond
  • Weber, Donna
  • Maloney, David
  • Holmberg, Leona
  • Rajandran, Joseph
  • Breitz, Hazel
  • Ghalie, Richard
  • Champlin, Richard

publication date

  • May 1, 2003

Research

keywords

  • Hematopoietic Stem Cell Transplantation
  • Holmium
  • Multiple Myeloma
  • Organophosphorus Compounds
  • Radioisotopes

Identity

Scopus Document Identifier

  • 0141593495

Digital Object Identifier (DOI)

  • 10.1182/blood-2002-10-3250

PubMed ID

  • 12730103

Additional Document Info

volume

  • 102

issue

  • 7