J Clin Oncol 2016 11 31;34(33):4015-4022. Epub 2016 Oct 31.
Sergio Cortelazzo, Atto Billio, Andrea Piccin, and Giovanni Negri, Ospedale Centrale di Bolzano, Bolzano; Corrado Tarella and Riccardo Bruna, Azienda Ospedaliera Ordine Mauriziano and University of Turin; Marco Ladetto and Manuela Zanni, Azienda Ospedaliera Universitaria (AOU) Città della Salute e della Scienza, Turin; Alessandro Massimo Gianni, Paolo Corradini, and Massimo Di Nicola, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, University of Milano; Andrés J.M. Ferreri, IRCCS San Raffaele Scientific Institute; Valentina Tabanelli and Stefano Pileri, Istituto Europeo di Oncologia; Alessandro Rambaldi, University of Milano, Milan; Anna Maria Barbui, Andrea Rossi, Giuseppe Gritti, Arianna Masciulli, Federica Delaini, Cristina Boschini, and Alessandro Rambaldi, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo; Caterina Patti and Antonino Mulé, Azienda Ospedali Riuniti Villa Sofia-Cervello, Palermo; Valerio Zoli, Ospedale San Camillo Forlanini, Rome; Claudia Castellino, Ospedale S. Croce e Carle, Cuneo; Francesco Di Raimondo, AOU Policlinico Vittorio Emanuele University of Catania, Catania; Fabio Benedetti, University of Verona; Marco Chilosi, Azienda Ospedaliera Universitaria Integrata Verona, Verona; Giorgio La Nasa, Ospedale Binaghi, Cagliari; Guido Gini, Ospedali Riuniti, Ancona; Livio Trentin, Azienda Ospedaliera-Università di Padova, Padua; Maurizio Frezzato, Ospedale San Bortolo, Vicenza; Leonardo Flenghi, Azienda Ospedaliera di Perugia, Perugia; and Simona Falorio, Ospedale Civile Spirito Santo, Pescara, Italy.
Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.