Effect of rituximab (R) on clinical outcomes after autologous stem cell transplantation (ASCT) in pts with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)

Abstract

8122 Background: First-line chemotherapy cures ∼50% of pts with DLBCL, while salvage therapy followed by ASCT can cure another ∼30%. R significantly improves response rates to 1st line therapy. This retrospective study was designed to test the hypotheses that: 1) ASCT is effective in pts relapsed after R-chemotherapy and 2) addition of R to salvage improves outcomes after ASCT. Methods: We identified 84 pts with relapsed/refractory DLBCL who underwent ASCT at our institution between 1990 and 2006. In all, 32% received a R-chemo 1st line regimen and 27% received R with salvage. The median age at ASCT was 49 yrs and the median time from diagnosis to ASCT was 16 mos. High-dose regimens included BCV (48%), BEAM (8%) and alkylator/TBI (20%). Results: Overall response rate (ORR) after ASCT was 52%, with 37% of pts in CR by day 100. Among those in CR, 16% had a CR pre-ASCT, 72% had a lesser response, and 9% were chemo-resistant. The addition of R to salvage (23/84 pts) was favorably associated with ORR after ASCT (OR: 5.2, 95% CI: 1.1 - 25, p=0.029), even in pts who had failed a prior R regimen (p=0.013). Other factors favorably associated with ORR were response to salvage (p=0.046) and time to ASCT >12 mos (p=0.017). At last f/u (med: 22 mos, iqr: 7 - 55 mos), event-free (EFS) and overall survival (OS) were both 35%. The only factor associated with EFS and OS in univariate and multivariate analyses was ORR after ASCT (HR: 0.16, 95% CI: 0.07 - 0.37, p<0.001 and HR: 0.12, 95% CI: 0.05 - 0.28, p<0.001 respectively). Age at ASCT, time to ASCT, year of ASCT, mobilization/conditioning regimen, and failure of a R-chemo regimen were not associated with EFS or OS. Conclusions: Pts with DLBCL who have failed a R-chemo first-line regimen derive an equal benefit from ASCT as pts who are R-naïve, with significant long-term EFS and OS. Additionally, inclusion of R in salvage therapy prior to ASCT provides superior response rates, even after a failed prior R-chemo regimen. These results confirm the benefit of ASCT for pts with DLBCL in the rituximab era and argue for the incorporation of R and related agents in studies of high-dose therapy and ASCT. No significant financial relationships to disclose.