First-in-human ²¹¹At-CD45 study sets dose limit before allogeneic transplant

Relapse remains a major cause of failure after allogeneic hematopoietic cell transplantation (HCT) for aggressive hematologic malignancies. In this two-stage dose-finding study, 45 adults aged 38–74 years at high risk of relapse from myeloid malignancies or acute leukemia received a single infusion of ²¹¹At-labeled anti-CD45 antibody before fludarabine and 2–3 Gy total-body irradiation, followed by HCT from matched or single-allele–mismatched donors.

In stage I, 17 patients received doses of 85–591 μCi/kg. Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) in the patient treated at 591 μCi/kg led investigators to set 500 μCi/kg as the protocol-defined maximum tolerated dose. In stage II, six of 28 patients treated at that dose developed VOD/SOS; all six were receiving sirolimus for graft-versus-host disease prophylaxis after unrelated-donor HCT. Infusion reactions were mild, and the treatment did not delay hematopoietic recovery or impair donor chimerism. Blasts cleared before conditioning in 12 of 13 patients with circulating blasts at baseline.

Estimated one-year relapse-free survival was 42% (95% CI, 28%–56%) and overall survival was 49% (95% CI, 34%–62%). These first-in-human findings establish feasibility but identify liver toxicity as a dose-limiting concern. The authors support phase II evaluation; the results do not establish a change in transplant practice.