Waldmann, Thomas A.; White, Jeffrey D.; Carrasquillo, Jorge A.; Reynolds, James C.; Paik, Chang H.; Gansow, Otto A.; Brechbiel, Martin W.; Jaffe, Elaine S.; Fleisher, Thomas A.; Goldman, Carolyn K.; Top, Lois E.; Bamford, Richard; Zaknoen, Sara; Roessler, Eric; Kasten Sportes, Claude; England, Richard; Litou, Hariklia; Johnson, John A.; Jackson White, Terri; Manns, Angela; Hanchard, Barrie; Junghans, Richard P.; Nelson, David L.....
Author Affiliation, Ana.
Radioimmunotherapy of Interleukin-2R - Expressing adult T-cell leukemia with yttrium-90-labeled anti-tac.
Date of Publication
Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive leukemia with a median survival time of 9 months; no chemotherapy regimen appears successful in inducing long-term disease-free survival. The scientific basis of the present study is that ATL cells express high-affinity interleukin-2 receptors identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference, anti-Tac armed with Yttrium-(90Y) was administered to 18 patients with ATL initially (first 9 patients) in a phase I dose-escalation trial and subsequently (second group of 9 patients) in a phase II trial involving a uniform 10-mCi dose of 90Y-labeled anti-Tac. Patients undergoing a remission were permitted to receive up to eight additional doses. At the 5- to 15-mCi doses used, 9 of 16 evaluable patients responded to 90Y anti-Tac with a partial (7 patients) or complete (2 patients) remission. The responses observed represent improved efficacy in terms of length of remission when compared with previous results with unmodified anti-Tac. Clinically meaningful (grade 3) toxicity was largely limited to the hematopoietic system. In conclusion, radioimmunotherapy with 90Y anti-Tac directed toward the IL-2R expressed on ATL cells may provide a useful approach for treatment of this aggressive malignancy.....