Page 275 - Haematologica - Vol. 105 n. 6 - June 2020

90Y-Anti-CD45 Antibody for Leukemia/Myelodysplasia
abnormalities, and the remaining seven patients had intermediate-risk cytogenetic abnormalities. The median HCT-comorbidity index of the 15 treated patients was three (range 0-7).
Three patients had HLA-matched related donors, and 12 had unrelated donors, of which ten were 10/10 HLA- matched, one was HLA-A antigen mismatched, and one had an allele mismatch at HLA-DQ.
The patients received an average of 78.6 mCi of 90Y (range 22.8-151.2 mCi), with average delivered doses of 10.5 Gy to marrow, 70 Gy to spleen, and 17.9 Gy to liver through complete radionuclide decay. Although a maxi- mum dose of 30 Gy was delivered to the liver, no DLT was observed; therefore, the MTD could not be estimat- ed. Despite the lack of any DLT observed among the 15 patients treated, the BC8 antibody was not labeled with higher amounts of 90Y that would deliver more than 30 Gy to any critical normal organ because of concerns of poten- tial damage to the antibody avidity and function.
Dosimetry, biodistribution and engraftment
Since the biokinetics of 90Y-labeled anti-CD45 antibody vary substantially from one patient to another, treatment planning based on individualized patient dosimetry enables a therapy that maximizes therapeutic efficacy without exceeding normal organ toxicity. The mean absorbed dose per unit administered activity (cGy/mCi ±standard deviation) for the 15 treated patients was: 15.25±7.05 to the bone marrow, 24.99 ± 6.76 to liver, 106.1 ± 33.19 to spleen, 8.14 ± 4.79 to kidney, 6.69 ± 19.5 to lung, and 2.16 ± 0.55 to the total body (Figure 1 and Online Supplementary Table S1). The calculated absorbed doses of 90Y to liver, marrow and spleen are summarized in Table 2.
Median CD34+ cell dose of the 15 transplanted patients was 9.03 (range 2.14-15.86) x106/kg. Median time to neu- trophil engraftment [absolute neutrophil count (ANC) >0.5 x 109/L for 3 consecutive days] was 15 (range 12-26) days. Median time to platelet engraftment (platelets >20 x109/L for 7 consecutive days without transfusion support) was 16.5 (range 12-74) days. All patients engrafted with median donor-derived CD3 chimerisms of 99% and
CD33 chimerisms of 100% by day 28, with 100% median donor-derived CD3 and CD33 chimerisms for both by day 84 after HCT.
Table 1. Characteristics of 15 patients who received a therapeutic dose of 90Y-DOTA-BC8.
Median age, [years (range)]
Sex Male
Female
Diagnosis at HCT AML, total n
Secondary AML, total n Refractory disease In CR1 with (+) MRD In CR2 with (+) MRD Rel 1
Primary AML, total n Rel1
Rel 2 MDS-RAEB, total n
Refractory disease
In CR1 with (+) MRD
Untreated CMML
History of previous allo-HCT Cytogenetic risk
Intermediate High/unfavorable
Donor status Related
Unrelated
62 (37-76)
8 7
10 7 1 4 1 1 3 1 2 4 3 1 1
3
7 8
3
12
3 (1-6) 4 (3-6) 1 (1-2) 0
Median n. pre-HCT induction chemotherapy [n, (range)] AML
Secondary
Primary MDS-RAEB
CMML
HCT: allogeneic hematopoietic cell transplantation; AML: acute myeloid leukemia; CR1: first complete remission; CR2: second CR; MRD: measurable residual disease; CR: complete remission; Rel: relapse; MDS-RAEB: myelodysplastic syndrome-refractory anemia with excess blasts; CMML: chronic myelomonocytic leukemia; n: number.
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Figure 1. Estimated radiation absorbed doses per millicurie of 90Y administered for 15 patients who received a therapeu- tic dose of 90Y-DOTA-BC8.