Phase I Study of a CD45-Targeted Antibody-Radionuclide Conjugate for High-Risk Lymphoma.
Clinical cancer research : an official journal of the American Association for Cancer Research
PURPOSE: External-beam radiation is the single most effective therapy for localized lymphoma. However, toxicity limits its use for multifocal disease. We evaluated CD45 as a therapeutic target for an antibody-radionuclide conjugate (ARC) for the treatment of lymphoma based on its ubiquitous expression, infrequent antigen loss or blockade, and the ability to target minimal disease based on panhematopoietic expression.
EXPERIMENTAL DESIGN: We performed a phase I trial of escalating doses of single-agent CD45-targeted ARC based on per-patient dosimetry using the BC8 antibody labeled with iodine-131 (
RESULTS: Sixteen patients were enrolled: 7 patients had B-NHL, 6 had HL, and 3 had T-NHL. Median number of prior therapies was 3 (range: 2-12). Absorbed doses up to 32 Gy to liver were delivered. No dose-limiting toxicities occurred. Non-hematologic toxicity was infrequent and manageable. Objective responses were seen across histologies. Fourteen patients had measurable disease at enrollment, 57% of whom achieved complete remission (CR), including all 3 with T-NHL. Three patients with B-NHL treated among the highest dose levels (26-32 Gy) remain in CR without subsequent therapy 35-41 months later.
CONCLUSIONS: CD45-targeted ARC therapy is well-tolerated at doses up to at least 32 Gy to the liver. Objective responses and long-term remissions were observed in patients with relapsed/refractory lymphoma. These data validate continued evaluation of anti-CD45 ARCs in lymphoma.
Cassaday, Ryan D; Press, Oliver W; Pagel, John M; Rajendran, Joseph G; Gooley, Ted A; Fisher, Darrell R; Holmberg, Leona A; Miyaoka, Robert S; Sandmaier, Brenda M; Green, Damian J; and Gopal, Ajay K, "Phase I Study of a CD45-Targeted Antibody-Radionuclide Conjugate for High-Risk Lymphoma." (2019). Articles, Abstracts, and Reports. 2183.