Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia.
Outcomes of patients with persistent high-risk leukemia or myelodysplasia prior to allogeneic hematopoietic cell transplantation are dismal. We therefore conducted a phase I trial evaluating the use of CD45-targeted radiotherapy preceding hematopoietic cell transplantation with the goal to improve outcomes for this high-risk scenario. Fifteen patients, median age of 62 (range 37-76) years, were treated (10 with advanced acute myeloid leukemia, 5 with high-risk myelodysplastic syndrome). All patients had evidence of disease prior to treatment including nine with marrow blast counts ranging from 7-84% and 6 with minimal residual disease. Patients received escalating doses of yttrium-90-labeled anti-CD45 antibody followed by fludarabine and 2 Gy total body irradiation prior to human leukocyte antigen-matched, related or unrelated hematopoietic cell transplantation. Although a maximum dose of 30 Gy was delivered to the liver, no dose-limiting toxicity was observed. Therefore, the maximum-tolerated dose could not be estimated. Treatment led to complete remission in 13 patients (87%). All patients engrafted by day 28. Six patients relapsed, median of 59 (range 6-351) days, after transplantation. The 1-year estimate of relapse was 41%. Eight patients (53%) are surviving with median follow-up of 1.8 (range 0.9-5.9) years. Estimated overall survival at 1 and 2 years was 66% and 46%, respectively, with progression-free survival estimated to be 46% at each time point. In conclusion, the combination of 90Y-DOTA-BC8 with an allogeneic hematopoietic cell transplantation regimen was feasible and tolerable. This approach appears promising in this high-risk leukemia/myelodysplasia patient population with active disease. Clinicaltrials.gov identifier: NCT01300572.
Vo, Phuong; Gooley, Ted A; Rajendran, Joseph G; Fisher, Darrell R; Orozco, Johnnie J; Green, Damian J; Gopal, Ajay K; Haaf, Robyn; Nartea, Margaret; Storb, Rainer; Appelbaum, Frederick R; Press, Oliver W; Pagel, John M; and Sandmaier, Brenda M, "Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia." (2019). Articles, Abstracts, and Reports. 2257.