Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia

Phuong Vo, Ted A Gooley, Joseph G Rajendran, Darrell R Fisher, Johnnie J Orozco, Damian J Green, Ajay K Gopal, Robyn Haaf, Margaret Nartea, Rainer Storb, Frederick R Appelbaum, Oliver W Press, John M Pagel, Brenda M Sandmaier, Phuong Vo, Ted A Gooley, Joseph G Rajendran, Darrell R Fisher, Johnnie J Orozco, Damian J Green, Ajay K Gopal, Robyn Haaf, Margaret Nartea, Rainer Storb, Frederick R Appelbaum, Oliver W Press, John M Pagel, Brenda M Sandmaier

Abstract

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 of improving outcomes for this high-risk scenario. Fifteen patients, median age 62 (range 37-76) years, were treated: ten with advanced acute myeloid leukemia, five 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 six 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 one and two 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. (Trial registered at clinicaltrials.gov identifier: NCT01300572).

Copyright© 2020 Ferrata Storti Foundation.

Figures

Figure 1.
Figure 1.
Estimated radiation absorbed doses per millicurie of 90Y administered for 15 patients who received a therapeutic dose of 90Y-DOTA-BC8.
Figure 2.
Figure 2.
Estimates of the probability of overall survival, relapse-free survival, and relapse among all patients who received a therapeutic dose of 90Y-DOTA-BC8 followed by total body irradiation/fludarabine. HCT: allogeneic hematopoietic cell transplantation.

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