Page 273 - Haematologica - Vol. 105 n. 6 - June 2020

Cell Therapy & Immunotherapy
Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia
Phuong Vo,1,2 Ted A. Gooley,1,2 Joseph G. Rajendran,3 Darrell R. Fisher,4 Johnnie J. Orozco,1,2 Damian J. Green,1,2 Ajay K. Gopal,1,2 Robyn Haaf,1 Margaret Nartea,1 Rainer Storb,1,2 Frederick R. Appelbaum,1,2 Oliver W. Press,1,2,† John M. Pagel5° and Brenda M. Sandmaier1,2
1Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle; 2Department of Medicine, University of Washington, Seattle; 3Department of Radiology, University of Washington, Seattle; 4Versant Medical Physics and Radiation Safety, Richland and 5Swedish Cancer Institute, Seattle, WA, USA
°Current address: Swedish Medical Center, Seattle, WA, USA †Posthumous.
ABSTRACT
Outcomes of patients with persistent high-risk leukemia or myelodys- plasia prior to allogeneic hematopoietic cell transplantation are dis- mal. 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 mar- row 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 trans- plantation. 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, medi- an 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 fea- sible and tolerable. This approach appears promising in this high-risk leukemia/myelodysplasia patient population with active disease. (Trial reg- istered at clinicaltrials.gov identifier: NCT01300572.)
Introduction
Allogeneic hematopoietic cell transplantation (HCT) is a commonly used therapy for patients with refractory/relapsed acute leukemia and myelodysplastic syndrome (MDS) with unfavorable genetics. Although HCT is the most effective treatment for these patients, the procedure is associated with significant toxicities, especially for elderly patients. Reduced-intensity preparative regimens have been developed as an alternative approach for older patients and those with comorbidities that might pre- vent them from undergoing a myeloablative HCT. Standard reduced-intensity condi- tioning regimens, however, have been commonly associated with higher relapse rates
Ferrata Storti Foundation
Haematologica 2020 Volume 105(6):1731-1737
Correspondence:
BRENDA M. SANDMAIER
bsandmai@fredhutch.org
Received: June 13, 2019. Accepted: October 3, 2019. Pre-published: October 3, 2019.
doi:10.3324/haematol.2019.229492
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/6/1731
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