title: 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.affiliation: Divisione Universitaria di Ematologia, Cattedra di Ematologia, Torino, Italy. marco.ladetto@unito.it
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Federica
authors.initials: F
authors.lastname: De Marco
authors.forename: Fabio
authors.initials: F
authors.lastname: Benedetti
authors.forename: Umberto
authors.initials: U
authors.lastname: Vitolo
authors.forename: Caterina
authors.initials: C
authors.lastname: Patti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pulsoni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Musso
authors.forename: Anna M
authors.initials: AM
authors.lastname: Liberati
authors.forename: Attilio
authors.initials: A
authors.lastname: Olivieri
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallamini
authors.forename: Enrico
authors.initials: E
authors.lastname: Pogliani
authors.forename: Delia
authors.initials: D
authors.lastname: Rota Scalabrini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Callea
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pavone
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tucci
authors.forename: Sergio
authors.initials: S
authors.lastname: Cortelazzo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Levis
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Ignazio
authors.initials: I
authors.lastname: Majolino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pileri
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
authors.forename: Roberto
authors.initials: R
authors.lastname: Passera
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D000069283:Rituximab; D016879:Salvage Therapy; D016019:Survival Analysis; D014182:Transplantation, Autologous; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab