Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas

• Published in: Journal of clinical oncology Vol. 34; no. 33; pp. 4015 - 4022
• Main Authors: Cortelazzo, Sergio, Tarella, Corrado, Gianni, Alessandro Massimo, Ladetto, Marco, Barbui, Anna Maria, Rossi, Andrea, Gritti, Giuseppe, Corradini, Paolo, Di Nicola, Massimo, Patti, Caterina, Mulé, Antonino, Zanni, Manuela, Zoli, Valerio, Billio, Atto, Piccin, Andrea, Negri, Giovanni, Castellino, Claudia, Di Raimondo, Francesco, Ferreri, Andrés J M, Benedetti, Fabio, La Nasa, Giorgio, Gini, Guido, Trentin, Livio, Frezzato, Maurizio, Flenghi, Leonardo, Falorio, Simona, Chilosi, Marco, Bruna, Riccardo, Tabanelli, Valentina, Pileri, Stefano, Masciulli, Arianna, Delaini, Federica, Boschini, Cristina, Rambaldi, Alessandro
• Format: Journal Article
• Language: English
• Published: United States 20.11.2016
• Subjects: Adolescent; Adult; Aged; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Combined Modality Therapy; Cyclophosphamide - therapeutic use; Doxorubicin - therapeutic use; Female; Humans; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - therapy; Male; Middle Aged; Prednisone - therapeutic use; Rituximab - administration & dosage; Stem Cell Transplantation; Treatment Outcome; Vincristine - therapeutic use; Young Adult
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2016.67.2980

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.