title: Consolidation anti-CD22 fractionated radioimmunotherapy with90Y-epratuzumab tetraxetan following R-CHOP in elderly patients with diffuse large B-cell lymphoma: a prospective, single group, phase 2 trial.
abstract: BACKGROUND
  Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated radioimmunotherapy using anti-CD2290Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma.
  
  
  METHODS
  We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals. Eligible patients were aged 60-80 years with bulky stage 2-3 or stage 3-4 CD20-positive diffuse large B-cell lymphoma, previously untreated, and not eligible for transplantation. Patients received six cycles of R-CHOP (rituximab [375 mg/m2], cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], and vincristine [1·4 mg/m2, up to 2 mg] all on day 1, and prednisone [40 mg/m2] daily for 5 days), administered every 14 days. 6-8 weeks after R-CHOP, responders received two doses of 15 mCi/m2(555 MBq/m2)90Y-epratuzumab tetraxetan administered 1 week apart. The primary endpoint was 2 year event-free survival in all registered eligible patients who received at least 1 day of study treatment; the safety analysis was done in the same population. This trial is registered with ClinicalTrials.gov, number NCT00906841.
  
  
  RESULTS
  Between Oct 22, 2008, and Dec 16, 2010, we recruited 75 patients, of whom four (5%) were excluded after central pathology review; hence, 71 (95%) patients were included in the analysis. All patients started induction treatment; 57 (80%) received radioimmunotherapy. With a median follow-up of 37 months (IQR 30-44), the estimated 2 year event-free survival was 75% (95% CI 63-84). Radioimmunotherapy toxicity consisted of grade 3-4 thrombocytopenia in 48 (84%) of 57 patients and neutropenia in 45 (79%) of 57 patients. One patient developed myelodysplastic syndrome 28 months after receiving radioimmunotherapy and one patient developed acute myeloid leukaemia 5 months after receiving radioimmunotherapy.
  
  
  CONCLUSIONS
  Fractionated radioimmunotherapy with90Y-epratuzumab tetraxetan might be appropriate for response consolidation after induction chemotherapy in older patients with advanced diffuse large B-cell lymphoma, but further comparative studies are needed.
  
  
  BACKGROUND
  Immunomedics, Amgen, Canceropôle Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements d'Avenir).
authors.affiliation: University Hospital, Nantes, France; Institut de Cancérologie de l'Ouest Cancer Center, Saint-Herblain, France. Electronic address: francoise.bodere@chu-nantes.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Kraeber-Bodere
authors.affiliation: University Hospital, Nantes, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Pallardy
authors.affiliation: Haematology Department, Hospital, La Roche sur Yon, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Maisonneuve
authors.affiliation: Institut de Cancérologie de l'Ouest Cancer Center, Saint-Herblain, France.
authors.forename: Loïc
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authors.lastname: Campion
authors.affiliation: University Hospital, Nantes, France.
authors.forename: Anne
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authors.lastname: Moreau
authors.affiliation: Institut Bergonié, Cancer Centre, and University of Bordeaux, Bordeaux, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Soubeyran
authors.affiliation: University Hospital, Nantes, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.affiliation: University Hospital, Clermont-Ferrand, France.
authors.forename: Olivier
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authors.affiliation: Jean Minjoz Hospital, Besançon, France.
authors.forename: Etienne
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authors.lastname: Daguindau
authors.affiliation: Centre Hospitalier Bretagne-Atlantique, Vannes, France.
authors.forename: Henry
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authors.lastname: Jardel
authors.affiliation: Catherine de Sienne Center, Nantes, France.
authors.forename: Nadine
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authors.lastname: Morineau
authors.affiliation: University Hospital Haut-Leveque, Bordeaux, France.
authors.forename: Krimo
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authors.lastname: Bouabdallah
authors.affiliation: Hematology and Cell Therapy Department, Clinical Investigation Center INSERM U1415, GICC UMR CNRS 7292, University Hospital, Tours, France.
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authors.lastname: Gyan
authors.affiliation: University Hospital, Angers, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Moles
authors.affiliation: University Hospital, Grenoble, France.
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authors.lastname: Gressin
authors.affiliation: University Hospital, Brest, France.
authors.forename: Christian
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authors.affiliation: Institut de Cancérologie de l'Ouest Cancer Center, Saint-Herblain, France.
authors.forename: Sophie
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authors.lastname: Sadot
authors.affiliation: Hôpital du Scorff, Lorient, France.
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authors.lastname: Moreau
authors.affiliation: Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Deau
authors.affiliation: University Hospital, Nantes, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bodet-Milin
authors.affiliation: Institut Bergonié, Cancer Centre, and University of Bordeaux, Bordeaux, France.
authors.forename: Anne-Laure
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authors.lastname: Cazeau
authors.affiliation: Eugène Marquis Cancer Center, Rennes, France.
authors.forename: Etienne
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authors.lastname: Garin
authors.affiliation: University Hospital, Brest, France.
authors.forename: Pierre-Yves
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authors.lastname: Salaun
authors.affiliation: University Hospital, Grenoble, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Vuillez
authors.affiliation: Hematology and Cell Therapy Department, Clinical Investigation Center INSERM U1415, GICC UMR CNRS 7292, University Hospital, Tours, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gouilleux-Gruart
authors.affiliation: Groupement d'Intêret Publique Arronax, Arronax, Saint-Herblain, France.
authors.forename: Jacques
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authors.lastname: Barbet
authors.affiliation: Clinical Research, Immunomedics, Morris Plains, NJ, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.affiliation: Clinical Research, Immunomedics, Morris Plains, NJ, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.affiliation: University Hospital, Rennes, France.
authors.forename: Thierry
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authors.lastname: Lamy
authors.affiliation: Institut Bergonié, Cancer Centre, and University of Bordeaux, Bordeaux, France.
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mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D016499:Radioimmunotherapy / Q000379:methods*; D000069283:Rituximab; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000074322:Antineoplastic Agents, Immunological; C497867:CD22 protein, human; C571759:R-CHOP protocol; D051918:Sialic Acid Binding Ig-like Lectin 2; D015021:Yttrium Radioisotopes; C448700:epratuzumab; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone