Background: The outcome of young DLBCL patients at high risk is not satisfactory with RCHOP. FIL conducted a multicenter randomized phase III trial, with a 2x2 factorial design, to compare two R-dose-dense chemotherapies, RCHOP14 (RC14) vs RMegaCHOP14 (RMC14), followed or not by HDC+ASCT (HDT). Patients and Methods: The main hypothesis was to test an increase of 2-year Progression-Free-Survival (PFS) from 50% in the standard arm (no-HDT) to 65% in the experimental arm (HDT); secondary comparison was between the two dose-dense regimens. Inclusion criteria were: age 18-65; untreated DLBC; aaIPI 2-3. Patients were stratified according aaIPI and randomized at diagnosis to receive: RC14 x 8; RMC14 x 6 (1200 mg/m2 Cyclophosphamide, 70 mg/m2 Doxorubicin, standard Vincristine/Prednisone); RC14 x 4 + HDT (R + high dose Cytarabine + Mitoxantrone + Dexamethasone + BEAM and ASCT); RMC14 x 4 + the same HDT. Results: From June 2005 to September 2010, 412 patients were enrolled and 399 were eligible: median age 49 (18-63); stage II/III/IV 6/29/65%; LDH >normal 89%, PS >1 43%, aaIPI 2/3 score 74/26%. At the time of this analysis, 375 are evaluable: 195 no-HDT and 180 HDT arm. Response rates were: CR 74%, PR 6%, NR 12%, toxic deaths 3% and 5% dropped out. Treatment-related deaths in no-HDT and HDT arm were: 2.6% and 3.3%. With a median follow-up of 23 months, 2-year PFS was 65% (95%CI:59-70). Two-year PFS for no-HDT vs HDT was: 59% (95%CI:51-57) vs 72% (95%CI:64-78), p .008 (Fig.1). Two-year PFS rates for RC14 vs RMC14 were superimposable. Two-year OS was 83% (95%CI: 78-87) with no differences between no-HDT and HDT. In a Cox-model, including the four arms, assuming RC14 as reference, the risk of relapse was significantly reduced mainly in RCHOP14+HDT arm (HR=0.47, 95%CI=0.27-0.81, p .007) with minor effect in RMegaCHOP14+HDT (HR=0.69, p .15) arm. Conclusions: this randomized trial showed that HDT, as first line treatment in young high risk DLBCL, significantly reduced the relapse rate in comparison to standard RCHOP14. A more aggressive dose-dense chemotherapy does not seem to play a significant role. So far, this advantage in PFS does not translate in overall survival differences. A longer follow-up will further clarify the role of HDT as first line treatment in this poor-prognosis DLBCL patients. 072 Figure 1. 2-year PFS for no-HDT vs HDT

A RANDOMIZED MULTICENTRE PHASE III STUDY FOR FIRST LINE TREATMENT OF YOUNG PATIENTS WITH HIGH RISK (AAIPI 2-3) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): RITUXIMAB (R) PLUS DOSE-DENSE CHEMOTHERAPY CHOP14/MEGACHOP14 WITH OR WITHOUT INTENSIFIED HIGH-DOSE CHEMOTHERAPY (HDC) AND AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT). RESULTS OF DLCL04 TRIAL OF ITALIAN LYMPHOMA FOUNDATION (FIL) / U., Vitolo; A., Chiappella; E., Brusamolino; E., Angelucci; M., Balzarotti; A. M., Carella; G., Ciccone; G., Gaidano; F., Merli; F., Pane; V., Pavone; G., Rossi; L., Rigacci; C., Stelitano; F., Zaja; Martelli, Maurizio. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 22 (suppl 4):(2011), pp. 106-106. ((Intervento presentato al convegno 11th International Conference on Malignant Lymphoma tenutosi a Lugano, SWITZERLAND nel JUN 15-18, 2011 [10.1093/annonc/mdr197].

A RANDOMIZED MULTICENTRE PHASE III STUDY FOR FIRST LINE TREATMENT OF YOUNG PATIENTS WITH HIGH RISK (AAIPI 2-3) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): RITUXIMAB (R) PLUS DOSE-DENSE CHEMOTHERAPY CHOP14/MEGACHOP14 WITH OR WITHOUT INTENSIFIED HIGH-DOSE CHEMOTHERAPY (HDC) AND AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT). RESULTS OF DLCL04 TRIAL OF ITALIAN LYMPHOMA FOUNDATION (FIL)

MARTELLI, Maurizio
2011

Abstract

Background: The outcome of young DLBCL patients at high risk is not satisfactory with RCHOP. FIL conducted a multicenter randomized phase III trial, with a 2x2 factorial design, to compare two R-dose-dense chemotherapies, RCHOP14 (RC14) vs RMegaCHOP14 (RMC14), followed or not by HDC+ASCT (HDT). Patients and Methods: The main hypothesis was to test an increase of 2-year Progression-Free-Survival (PFS) from 50% in the standard arm (no-HDT) to 65% in the experimental arm (HDT); secondary comparison was between the two dose-dense regimens. Inclusion criteria were: age 18-65; untreated DLBC; aaIPI 2-3. Patients were stratified according aaIPI and randomized at diagnosis to receive: RC14 x 8; RMC14 x 6 (1200 mg/m2 Cyclophosphamide, 70 mg/m2 Doxorubicin, standard Vincristine/Prednisone); RC14 x 4 + HDT (R + high dose Cytarabine + Mitoxantrone + Dexamethasone + BEAM and ASCT); RMC14 x 4 + the same HDT. Results: From June 2005 to September 2010, 412 patients were enrolled and 399 were eligible: median age 49 (18-63); stage II/III/IV 6/29/65%; LDH >normal 89%, PS >1 43%, aaIPI 2/3 score 74/26%. At the time of this analysis, 375 are evaluable: 195 no-HDT and 180 HDT arm. Response rates were: CR 74%, PR 6%, NR 12%, toxic deaths 3% and 5% dropped out. Treatment-related deaths in no-HDT and HDT arm were: 2.6% and 3.3%. With a median follow-up of 23 months, 2-year PFS was 65% (95%CI:59-70). Two-year PFS for no-HDT vs HDT was: 59% (95%CI:51-57) vs 72% (95%CI:64-78), p .008 (Fig.1). Two-year PFS rates for RC14 vs RMC14 were superimposable. Two-year OS was 83% (95%CI: 78-87) with no differences between no-HDT and HDT. In a Cox-model, including the four arms, assuming RC14 as reference, the risk of relapse was significantly reduced mainly in RCHOP14+HDT arm (HR=0.47, 95%CI=0.27-0.81, p .007) with minor effect in RMegaCHOP14+HDT (HR=0.69, p .15) arm. Conclusions: this randomized trial showed that HDT, as first line treatment in young high risk DLBCL, significantly reduced the relapse rate in comparison to standard RCHOP14. A more aggressive dose-dense chemotherapy does not seem to play a significant role. So far, this advantage in PFS does not translate in overall survival differences. A longer follow-up will further clarify the role of HDT as first line treatment in this poor-prognosis DLBCL patients. 072 Figure 1. 2-year PFS for no-HDT vs HDT
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/484988
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 10
social impact