Affiliation:
1. From the Service des Maladies du Sang, Centre Hospitalier Regional, L'Universitaire de Lille; Institut de Biologie, L'Institut National de la Santé et de la Recherche Médicale Unit 892, Centre de Recherche en Cancérologie Nantes-Angers; Centre Hospitalier Universitaire, Nantes; Centre René Gauducheau, Institut Régional du Cancer Nantes-Atlantique, Nantes-Saint-Herblain, France; Immunomedics, Morris Plains; Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ; Georg...
Abstract
Purpose Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL). Patients and Methods A multicenter trial evaluated two or three weekly infusions of yttrium-90 (90Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. Results At the maximum total 90Y dose of 45 mCi/m2 (1,665 MBq/m2), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and 90Y doses, even in poor-risk categories (refractory to last anti-CD20–containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total 90Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m2 total 90Y-dose [1,110 MBq/m2]). Further, patients with FL refractory to prior anti-CD20–containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. Conclusion Fractionated anti-CD22 radioimmunotherapy provides high total doses of 90Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m2 × 2 weeks as the recommended dose for future studies.
Publisher
American Society of Clinical Oncology (ASCO)
Cited by
102 articles.
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