Addition of Rituximab to CHOP Chemotherapy Significantly Improves Survival of Patients with Transformed Lymphoma.

Abstract

Background: Transformation of indolent lymphoma into diffuse large B-cell lymphoma (DLBCL) has been associated with poor survival and the optimal therapy is unknown. The addition of rituximab to CHOP chemotherapy (CHOP-R) has been shown to significantly improve the survival of patients (pts) with de novo DLBCL. However, the impact of rituximab on the survival of patients with transformed DLBCL remains unknown. Methods: As part of a large retrospective analysis examining the long term natural history of pts initially diagnosed with indolent lymphoma in British Columbia (B.C.) (n=690; follicular 600, small lymphocytic 49, lymphoplasmacytic 41), we have identified those pts who developed transformed lymphoma. The definition of transformation was based on either histological confirmation or clinical features, defined as one or more of the following: rapid discordant nodal or extranodal growth; sudden rise in LDH to > 2 x previous baseline; involvement of unusual extranodal sites; or hypercalcemia. Pts were excluded from this analysis if they received high-dose chemotherapy and stem cell transplant as part of the treatment for their transformed lymphoma (n= 9). Pts who were too frail to be treated with multi-agent chemotherapy were also excluded. The extent of disease at transformation was considered limited in pts with single nodal region involvement, no B symptoms, non-bulky disease (<10 cm) and with limited extranodal involvement. Pts with more extensive disease were considered to have advanced transformation. Results: 108 pts with transformed lymphoma were identified in the B.C. lymphoid database, the majority of whom had a prior history of follicular lymphoma (n=103, 95%). Median age at transformation was 60 y (22–71). Transformation was histologically confirmed in 74 (69%) pts. The outcome of 23 pts who were treated with CHOP-R was compared to 85 pts who were treated with CHOP-like chemotherapy. None of the 108 pts had received rituximab as part the management of their indolent lymphoma. The median follow-up for all living pts in the CHOP-like cohort was 7 y (3–14) and 3 y (0.5–5) in the CHOP-R cohort. The post-transformation 5 y overall survival following CHOP-like chemotherapy was 33% vs 61% after CHOP-R (P= 0.01). This difference in survival remained significant when pts with clinically diagnosed transformation were excluded from the analysis (P= 0.02). For the 78 pts with advanced disease extent (59, CHOP-like; 19, CHOP-R) there was a significant difference in PT-5yOS (21% vs 57%, respectively; P= 0.005). For pts with limited disease extent (CHOP-like, 26; CHOP-R, 4) no significant difference in PT-5yOS was observed (P= 0.2). Conclusions: In rituximab-naive patients with indolent lymphoma, the addition of rituximab to CHOP chemotherapy significantly improves overall survival after transformation.