title: Rituximab plus CHOP (R-CHOP) overcomes bcl-2--associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL).
abstract: In diffuse large B-cell lymphoma (DLBCL), the combination of rituximab and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisone; R-CHOP) has been shown to be more effective than CHOP for the treatment of elderly patients. Bcl-2 protein expression has been associated with poor prognosis in patients with DLBCL. To establish whether or not rituximab reduces bcl-2-associated treatment failure, we studied bcl-2 protein expression and clinical outcome in patients included in the Groupe d'Etude des Lymphomes de l'Adulte LNH-98-5 trial. Patients between 60 and 80 years of age were randomized to receive 8 cycles of either CHOP or R-CHOP every 3 weeks. Of the 399 patients included, 292 with histologically proven DLBCL had material available for bcl-2 study. Tumors were considered positive when at least 50% of tumor cells expressed bcl-2 protein. There were 193 (66%) bcl-2+ patients and 99 (34%) bcl-2- patients. The response rates for R-CHOP and CHOP were, respectively, 78% and 60% (P =.01) in bcl-2+ patients and 76% and 73% (P =.7) in bcl-2- patients. At a median of 2 years of follow-up, R-CHOP was significantly associated with a better overall survival than CHOP in bcl-2+ patients (67% +/- 9% versus 48% +/- 11%, P =.004). In bcl-2- patients there was no statistically significant difference (72% +/- 12% versus 67% +/- 14%, P =.6). In addition, R-CHOP was associated with significantly better event-free survival than CHOP in bcl-2+ patients (58% +/- 10% versus 32% +/- 10%, P <.001) but not in bcl-2- patients (60% +/- 13% versus 40% +/- 15%, P =.13). Multivariate analysis confirmed the significant benefit for survival and event-free survival of R-CHOP in bcl-2+ patients. These results suggest that rituximab is able to prevent chemotherapy failure in patients with bcl-2 protein overexpression.
authors.affiliation: Service d'Onco-Hématologie, INSERM ERM0220-Hôpital Saint Louis, AP-HP, Paris, France. nicolas.mounier@sls.ap-hop-paris.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
authors.forename: Josette
authors.initials: J
authors.lastname: Briere
authors.forename: Christian
authors.initials: C
authors.lastname: Gisselbrecht
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Emile
authors.forename: Pierre
authors.initials: P
authors.lastname: Lederlin
authors.forename: Catherine
authors.initials: C
authors.lastname: Sebban
authors.forename: Francoise
authors.initials: F
authors.lastname: Berger
authors.forename: Andre
authors.initials: A
authors.lastname: Bosly
authors.forename: Pierre
authors.initials: P
authors.lastname: Morel
authors.forename: Herve
authors.initials: H
authors.lastname: Tilly
authors.forename: Reda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: Felix
authors.initials: F
authors.lastname: Reyes
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000188:drug therapy / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000502:physiology*; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D019253:Proto-Oncogene Proteins c-bcl-2; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone