Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias. Academic Article uri icon

Overview

abstract

  • PURPOSE: Mouse monoclonal antibody (mAb) M195 (anti-CD33) is reactive with most myeloid leukemia cells, monocytes, and hematopoietic progenitors, but not with other hematopoietic cells or stem cells nor with nonhematopoietic human tissues. A therapeutic dose-escalation study of M195 labeled with iodine 131 was conducted in patients with relapsed or refractory myeloid leukemias. METHODS: Twenty-four patients (16 relapsed or refractory acute myeloid leukemias, five blastic myelodysplastic syndromes [MDS], two chemotherapy-related secondary leukemias, and one blastic chronic myelogenous leukemia [CML]), including seven who had failed to respond to prior bone marrow transplantation (BMT), received from 50 mCi/m2 to 210 mCi/m2 of 131I-M195 in divided doses. RESULTS: In 22 patients, whole-body gamma-imaging demonstrated marked uptake of antibody into all areas of bone marrow. Twenty-three patients (96%) demonstrated decreases in peripheral-blood cell counts, with decreased percentage of bone marrow blasts seen in 83% of cases. Eighty-nine percent of bone marrow biopsies examined quantitatively demonstrated substantial decreases in the number of blasts, with greater than 99% of blasts killed in some patients. The two cases that failed to demonstrate leukemic cytoreduction occurred in the first two dose levels. For 131I doses of 135 mCi/m2 or greater, pancytopenia was profound and lasted for at least 12 days. Eight patients had sufficient marrow cytoreduction to proceed to BMT. Three of these achieved marrow remission, one of 6+, and one of 9 months' duration. Two patients in blastic phase temporarily reverted to their original myelodysplastic states. Thirty-seven percent of assessable patients developed human anti-mouse antibody (HAMA). In two patients with HAMA who were re-treated, plasma 131I-M195 levels could not be maintained and no therapeutic effect resulted. Significant nonhematologic toxicity (hepatic) was seen in one patient and the maximum-tolerated dose (MTD) was not reached. CONCLUSION: These data suggest that safe leukemic cytoreduction can be achieved with 131I-M195 even in multiply relapsed or chemotherapy-refractory leukemias. This agent may be useful as part of a preparative regimen for BMT.

authors

  • Larson, Steven Mark
  • Schwartz, M A
  • Lovett, D R
  • Redner, Arlene
  • Finn, R D
  • Graham, M C
  • Divgi, C R
  • Dantis, Lucy
  • Gee, T S
  • Andreeff, Michael
  • Old, L J

publication date

  • February 1, 1993

Research

keywords

  • Antibodies, Monoclonal
  • Iodine Radioisotopes
  • Leukemia, Myeloid
  • Radioimmunotherapy

Identity

Scopus Document Identifier

  • 0027499283

Digital Object Identifier (DOI)

  • 10.1200/JCO.1993.11.2.294

PubMed ID

  • 8426207

Additional Document Info

volume

  • 11

issue

  • 2