Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage.

Abstract

In this randomized multicenter study of 136 patients, 6 courses of CHOP (cyclo-phosphamide/doxorubicin/vincristine/prednisone) followed by rituximab (CHOP-R) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting (R-HDS) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma (FL) after the introduction of monoclonal antibodies. The analysis was intention to treat with event-free survival (EFS) as the primary endpoint. Complete remission (CR) was 62% with CHOP-R and 85% with R-HDS (P < .001). At a median follow-up (MFU) of 51 months, the 4-year EFS was 28% and 61%, respectively (P < .001), with no difference in overall survival (OS). Molecular remission (MR) was achieved in 44% of CHOP-R and 80% of R-HDS patients (P < .001), and was the strongest independent outcome predictor. Patients relapsing after CHOP-R underwent salvage R-HDS in 71% of cases. Salvage R-HDS had an 85% CR rate and a 68% 3-year EFS (MFU, 30 months). We conclude that (1) achieving MR is critical for effective disease control, regardless of which treatment is used; (2) R-HDS ensures superior disease control and molecular outcome than CHOP-R, but no OS improvement; and (3) CHOP-R failures have a good outcome after salvage R-HDS, suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS-like treatments. This trial was registered at www.clinicaltrials.gov as no. NCT00435955.

• Authors: Marco Ladetto, Federica De Marco, Fabio Benedetti, Umberto Vitolo, Caterina Patti, Alessandro Rambaldi, Alessandro Pulsoni, Maurizio Musso, Anna M Liberati, Attilio Olivieri, Andrea Gallamini, Enrico Pogliani, Delia Rota Scalabrini, Vincenzo Callea, Francesco Di Raimondo, Vincenzo Pavone, Alessandra Tucci, Sergio Cortelazzo, Alessandro Levis, Mario Boccadoro, Ignazio Majolino, Alessandro Pileri, Alessandro M Gianni, Roberto Passera, Paolo Corradini, Corrado Tarella, Gruppo Italiano Trapianto di Midollo Osseo (GITMO), Intergruppo Italiano Linfomi (IIL)
• Journal: Blood (Blood) Vol. 111 Issue 8 Pg. 4004-13 (Apr 15 2008) ISSN: 0006-4971 [Print] United States
• PMID: 18239086 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Rituximab

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Feasibility Studies
• Female
• Humans
• Immunotherapy
• Kaplan-Meier Estimate
• Lymphoma, Follicular (diagnosis, drug therapy)
• Male
• Middle Aged
• Proportional Hazards Models
• Prospective Studies
• Risk Factors
• Rituximab
• Salvage Therapy
• Survival Analysis
• Transplantation, Autologous
• Treatment Failure
• Treatment Outcome