Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: a phase II multicenter study.
BACKGROUND
We investigated the addition of rituximab to dose-dense and high-dose chemotherapy with autologous stem cell transplantation in patients with untreated poor-prognosis diffuse large B-cell lymphoma.


METHODS
Ninety-four young patients (age, 18-60) with stage III-IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide-epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustine-etoposide-cytarabine-melphalan (BEAM) with autologous stem cell transplantation.


RESULTS
The complete response and toxic death rates were 82% and 5%, respectively. Failure-free survival and overall survival rates at 4 years were 73% and 80%, respectively. The outcomes of these patients were retrospectively compared to those of 41 patients with similar characteristics enrolled into a previous phase II trial of high-dose chemotherapy without rituximab. This historical group was treated with eight weekly infusions of methotrexate-doxorubicin-cyclophosphamide-vincristine-prednisone-bleomycin (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation. The 4-year failure-free survival rates for the rituximab and historical groups were 73% versus 44%, respectively (p=0.001); the 4-year overall survival rates were 80% and 54%, respectively (p=0.002). A Cox's multivariable model was applied to adjust the effect of treatment for unbalanced or important prognostic factors: failure and death risks were significantly reduced in the rituximab group compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01) for failure-free survival and 0.46 (p=0.02) for overall survival.


CONCLUSIONS
These results suggest that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and such regimens need to be compared to dose-dense chemoimmunotherapy without autologous stem cell transplantation in randomized trials.
Vitolo
Umberto
U
SC Ematologia II, Azienda Ospedaliera e Universitaria San Giovanni Battista, Corso Bramante 88, Turin, Italy. uvitolo@molinette.piemonte.it
Chiappella
Annalisa
A
Angelucci
Emanuele
E
Rossi
Giuseppe
G
Liberati
Anna Marina
AM
Cabras
Maria Giuseppina
MG
Botto
Barbara
B
Ciccone
Giovannino
G
Gaidano
Gianluca
G
Falchi
Lorenzo
L
Freilone
Roberto
R
Novero
Domenico
D
Orsucci
Lorella
L
Pavone
Vincenzo
V
Pogliani
Enrico
E
Rota-Scalabrini
Delia
D
Salvi
Flavia
F
Tonso
Anna
A
Tucci
Alessandra
A
Levis
Alessandro
A
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013997:Time Factors; D014182:Transplantation, Autologous
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab