title: High rates of durable responses with anti-CD22 fractionated radioimmunotherapy: results of a multicenter, phase I/II study in non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) 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 (90)Y dose of 45 mCi/m(2) (1,665 MBq/m(2)), 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 (90)Y 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 (90)Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m(2) total (90)Y-dose [1,110 MBq/m(2)]). 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.
  
  
  CONCLUSIONS
  Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.
authors.affiliation: Service des Maladies du Sang, Centre Hospitalier Regional, L'Universitaire de Lille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Morschhauser
authors.forename: Françoise
authors.initials: F
authors.lastname: Kraeber-Bodéré
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Petillon
authors.forename: Damien
authors.initials: D
authors.lastname: Huglo
authors.forename: Lorenz H
authors.initials: LH
authors.lastname: Trümper
authors.forename: Johannes
authors.initials: J
authors.lastname: Meller
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Carl-Martin
authors.initials: CM
authors.lastname: Kirsch
authors.forename: Ralph
authors.initials: R
authors.lastname: Naumann
authors.forename: Joachim
authors.initials: J
authors.lastname: Kropp
authors.forename: Heather
authors.initials: H
authors.lastname: Horne
authors.forename: Nick
authors.initials: N
authors.lastname: Teoh
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.forename: Caroline
authors.initials: C
authors.lastname: Bodet-Milin
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Chatal
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy; D016896:Treatment Outcome; D055815:Young Adult; D015021:Yttrium Radioisotopes / Q000008:administration & dosage*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015021:Yttrium Radioisotopes; C448700:epratuzumab