Estimating the impact of rituximab on bcl-2-associated resistance to CHOP using competing risks in elderly patients with diffuse large B-cell lymphoma (DLBCL)

Abstract

7514 Background: In diffuse large B-cell lymphoma, the combination of rituximab and CHOP (R-CHOP) has been proved to reduce bcl-2-associated treatment failure in elderly patients. However, some deaths could be due to age-associated morbidity such as cardio-vascular events. Patients and Methods: We therefore, addressed the question of its long-term impact by a competing risks analysis of 292 patients from the previously updated LNH-98–5 trial by the Groupe d’Etude des Lymphomes de l’Adulte (GELA) (Feugier et al, J Clin Oncol 2005). Using the competing risk formulation of Cox model regression, we investigated the effect of the explanatory variables on different competing events during the disease’s course such as progression, relapse, or death. Results: With a median follow-up of 5 years, R-CHOP was associated with a better survival than CHOP in 193 bcl-2-positive patients (56 ± 9% vs 42 ± 11%, P = 0.01), whereas in 99 bcl-2-negative patients there was no difference (58 ± 14% vs 52 ± 15% vs, P = 0.6). Results of competing risks analysis are given in table. Of particular interest, R-CHOP significantly decreased the risk of progression or relapse in both bcl-2-positive (RR = 2.6, P < 0.001) and bcl-2 negative (RR = 2.2, P = 0.01) and had no impact on the risk of death in complete remission patients (age over 70 remained an adverse factor). After relapse, aa-IPI 2–3 (RR = 2.9, P < 0.0001) and bcl-2 overexpression (RR = 1.5, P = 0.03) had still a significant effect on the risk of death but not front-line R-CHOP and age above 70. Conclusion: These findings highlight the role of rituximab in the sensitization to drug-induced apoptosis without inducing long-term sequel. However, Bcl2 positive patients failed to salvage treatment after relapse. [Table: see text] No significant financial relationships to disclose.