www.thelancet.com/haematology Published online December 7, 2016 http://dx.doi.org/10.1016/S2352-3026(16)30168-5 1 Articles Lancet Haematol 2016 Published Online December 7, 2016 http://dx.doi.org/10.1016/ S2352-3026(16)30168-5 See Online/Comment http://dx.doi.org/10.1016/ S2352-3026(16)30188-0 *Contributed equally University Hospital, Nantes, France (Prof F Kraeber-Bodere MD, A Pallardy MD, A Moreau MD, Prof S Le Gouill MD, C Bodet-Milin MD); Institut de Cancérologie de l’Ouest Cancer Center, Saint-Herblain, France (Prof F Kraeber-Bodere, L Campion MD, S Sadot MD); Haematology Department, Hospital, La Roche sur Yon, France (H Maisonneuve MD); Institut Bergonié, Cancer Centre, and University of Bordeaux, Bordeaux, France (I Soubeyran MD, A-L Cazeau MD, Prof P Soubeyran MD); University Hospital, Clermont-Ferrand, France (Prof O Tournilhac MD); Jean Minjoz Hospital, Besançon, France (E Daguindau MD); Centre Hospitalier Bretagne-Atlantique, Vannes, France (H Jardel MD); Catherine de Sienne Center, Nantes, France (N Morineau MD); University Hospital Haut- Leveque, Bordeaux, France (K Bouabdallah MD); Hematology and Cell Therapy Department, Clinical Investigation Center INSERM U1415, GICC UMR CNRS 7292, University Hospital, Tours, France (Prof E Gyan MD, V Gouilleux-Gruart PhD); University Hospital, Angers, France (M-P Moles MD); University Hospital, Grenoble, France (R Gressin MD, Consolidation anti-CD22 fractionated radioimmunotherapy with 90 Y-epratuzumab tetraxetan following R-CHOP in elderly patients with diffuse large B-cell lymphoma: a prospective, single group, phase 2 trial Françoise Kraeber-Bodere*, Amandine Pallardy*, Hervé Maisonneuve, Loïc Campion, Anne Moreau, Isabelle Soubeyran, Steven Le Gouill, Olivier Tournilhac, Etienne Daguindau, Henry Jardel, Nadine Morineau, Krimo Bouabdallah, Emmanuel Gyan, Marie-Pierre Moles, Remy Gressin, Christian Berthou, Sophie Sadot, Philippe Moreau, Bénédicte Deau, Caroline Bodet-Milin, Anne-Laure Cazeau, Etienne Garin, Pierre-Yves Salaun, Jean-Philippe Vuillez, Valérie Gouilleux-Gruart, Jacques Barbet, William A Wegener, David M Goldenberg, Thierry Lamy, Pierre Soubeyran Summary 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-CD22 ⁹⁰Y-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. Findings 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. Interpretation Fractionated radioimmunotherapy with ⁹⁰Y-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. Funding Immunomedics, Amgen, Canceropôle Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements d’Avenir). Introduction Chemoimmunotherapy combining rituximab with cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) represents the standard therapy for elderly patients with newly diagnosed diffuse large B-cell lymphoma. The addition of rituximab to CHOP has significantly improved overall survival in patients older than 60 years compared with CHOP alone. 1,2 The Groupe d’Etude des Lymphomes de l’Adulte 1 compared eight cycles of CHOP with eight cycles of R-CHOP, both given in 21 day cycles. The addition of rituximab improved overall survival in low-risk and high-risk age- adjusted International Prognostic Index groups, but 5 year overall survival still remained lower than 50% in high-risk patients. 1 In the Ricover 60 study 2 done by the Deutsche Studiengruppe Hochmaligne Lymphome, 1222 elderly patients with diffuse large B-cell lymphoma were randomly assigned to receive six or eight cycles of CHOP or R-CHOP, given in 14 day cycles. Of the four regimens tested, six cycles of R-CHOP were preferred since, compared with six cycles of CHOP, they improved 3 year progression-free survival (66% vs 47%) and overall survival (78% vs 68%), whereas continuation of chemotherapy beyond six cycles did not appear to improve outcome, even in partial responders. Finally, despite the improvement obtained by the addition of rituximab to first-line chemotherapy, the proportion of high-risk elderly patients who were cured