Phase I Study of a CD45-Targeted Antibody–Radionuclide Conjugate for High-Risk Lymphoma
Autor: | Darrell R. Fisher, Ajay K. Gopal, Brenda M. Sandmaier, John M. Pagel, Robert S. Miyaoka, Ted Gooley, Damian J. Green, Joseph G. Rajendran, Leona Holmberg, Ryan D. Cassaday, Oliver W. Press |
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Rok vydání: | 2019 |
Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Immunoconjugates medicine.medical_treatment Salvage therapy Article Iodine Radioisotopes Young Adult 03 medical and health sciences 0302 clinical medicine Refractory immune system diseases hemic and lymphatic diseases Internal medicine medicine Humans Combined Modality Therapy Young adult Survival rate Aged Salvage Therapy business.industry Lymphoma Non-Hodgkin Antibodies Monoclonal Middle Aged Radioimmunotherapy Prognosis medicine.disease Hodgkin Disease Lymphoma Survival Rate 030104 developmental biology 030220 oncology & carcinogenesis Toxicity Leukocyte Common Antigens Female Neoplasm Recurrence Local business Follow-Up Studies Stem Cell Transplantation |
Zdroj: | Clin Cancer Res |
ISSN: | 1557-3265 1078-0432 |
Popis: | 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. Patients and Methods: 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 (131I) followed by autologous stem cell support in adults with relapsed, refractory, or high-risk B-cell non-Hodgkin lymphoma (B-NHL), T-cell NHL (T-NHL), or Hodgkin lymphoma. The primary objective was to estimate the maximum tolerated radiation absorbed dose. Results: Sixteen patients were enrolled: 7 patients had B-NHL, 6 had Hodgkin lymphoma, and 3 had T-NHL. Median number of prior therapies was three (range: 2–12). Absorbed doses up to 32 Gy to liver were delivered. No dose-limiting toxicities occurred. Nonhematologic 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. |
Databáze: | OpenAIRE |
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