Prior Therapy with Rituximab Correlates with Less Acute Graft-Versus-Host Disease and Better Survival in B-Cell Lymphoma Patients Who Received Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT).
Authors: Ratanatharathorn Voravit , Horowitz Mary M. , Logan Brian , Arora Mukta , Wang Dan , Uberti Joseph P. , Gale Robert P. , Antin Joseph H. , Bornhaeuser Martin , Hale Gregory A. , Ringden Olle , Cairo Mitchell S. , Gupta Vikas , Cutler Corey , Anasetti Claudio , Pavletic Steven Z. 
Published: October 2019

Animal models of acute graft versus host disease (GVHD) suggested the critical role of host antigen-presenting cells (APC) in the pathogenesis of acute GVHD (Shlomchik et al Science285:412, 1999). Depletion of host B cells reduced the incidence of acute GVHD (Schultz et al BMT16:289, 1995). We hypothesized that B-cell depletion by prior rituximab (RTX) therapy in lymphoma pts might result in reduced incidence of acute GVHD (Ratanatharathorn et al Blood96:391a, 2000). We now analyzed the outcomes of allogeneic PBSCT in 435 B-cell lymphoma pts reported to CIBMTR from 1999 to 2004. Pts who had prior therapy with anti-CD52 or anti-T-cell antibody or recipients of conditioning regimens containing any of these antibodies were excluded. All patients received unmodified PBSC grafts. Pts were considered to have prior RTX therapy if they received RTX within 6 months of transplantation. There were 256 pts who did not receive RTX within 6 months of transplantation (No-RTX group) and 179 pts received RTX within 6 months of transplantation (RTX group). In RTX group, most pts (67%) received the last dose of RTX within 3 months of transplantation and 54% received at least two doses of RTX. Baseline characteristics of the two groups were similar except for significantly more unrelated donor (32% vs 19%, P=0.002)), tacrolimus use (47% vs 26%, P<0.001)), more recent year of transplant (87% vs 66% transplanted in 2001–2004, P<0.001) and shorter time from diagnosis to transplantation (22 vs 25 mos, P=0.04) in the RTX group. Median follow-up of survivors for the RTX group was 30 (3–82) mos and 39 (3–88) mos for the No-RTX group. One-yr progression-free survival for No-RTX and RTX groups were 54% (95% CI, 48–61%) and 66% (95% CI, 59–73%) (P=0.01), respectively. One-yr overall survival for No-RTX and RTX groups were 58% (95% CI, 52–64%) and 71% (95% CI, 64–77%) (P=0.009), respectively. Relative risks from multivariable analyses for the RTX group compared to the No-RTX group are shown in Table 1. In this study, prior RTX therapy correlates with less acute GVHD and similar rate of chronic GVHD. Prior RTX is also correlated with less transplant-related mortality (TRM) and better survival. There is no impact on disease progression or relapse. This study suggests the role of B cells in the pathogenesis of acute GVHD. Confirmatory studies of these observations are needed.

Clinical outcomes Relative risk (95% CI) P value Grade II-IV acute GVHD 0.72 (0.53–0.97) 0.03 Grade III-IV acute GVHD 0.55 (0.34–0.91) 0.02 Chronic GVHD 0.89 (0.67–1.18) 0.41 TRM 0.68 (0.46–1.0) 0.05 Progression or relapse 0.7 (0.42–1.19) 0.19 Progression-free survival 0.68 (0.50–0.92) 0.01 Overall survival 0.63 (0.46–0.86) 0.004