Radioimmunoconjugates in acute leukemia treatment: the future is radiant

Abstract

Targeted radiotherapy of the bone marrow using radiolabeled monoclonal antibodies is a therapeutic approach of considerable potential for the treatment of acute leukemia in addition to or as a substitute for total body irradiation. The data currently available, of about 300 patients, suggest that radioimmunotherapy (RIT) with beta-emitters in acute leukemia is feasible and safe using a variety of antibodies (anti-CD33, anti-CD45, anti-CD66) and radionuclides (131I, 90Y, 188Re). It appears to reduce the risk of relapse in high-risk acute myelogenous leukemia (AML) patients transplanted early in the course of their disease (<15% blasts) to 20-30%. Furthermore, it has shown the potential to safely intensify reduced-intensity conditioning regimens (nonrelapse mortality of 25% compared to relapse rate of 55% within 2 years). Significant improvements in the results of refractory patients will probably depend on the successful further development of RIT with alpha-emitters or the use of a cocktail of antibodies labeled with alpha- and beta-emitters, in a first dose escalation study of 213Bi-labeled anti-CD33 in refractory AML (partial) remission could be achieved in 5/18 patients. Randomized trials to evaluate the therapeutic efficacy of RIT in the context of stem cell transplantation have been initiated and the results are keenly anticipated.