High dose therapy (HDT) followed by autologous stem cell support has poor outcome in patients with primary progressive lymphoma or relapse after primary HDT due to high relapse rates and failure free survival below 20%. Allogeneic SCT may help these patients by exerting an GVL effect. Its use however, is followed by high incidence of severe GVHD and treatment related mortality (TRM) in this population. The anti-CD20 monoclonal antibody rituximab has been claimed to solve this problem. We initiated a randomized phase II study using intermediate conditioning (Fludarabine 125 mg/m2, Busulfan 12 mg/kg and cyclophosphamide 120 mg/kg) followed by GVHD prophylaxis with short term mycophenolat mofetil plus tacrolimus. Patients were randomized to receive two times four doses of rituximab (375 mg/m2) post transplant starting day +28 and day +175 or no further GVHD prophylaxis. Here we report the results of a first interim analysis. From January 2005 to August 2007 sixty patients (pts) with aggressive NHL were enrolled. Thirty one pts had diffuse large B cell NHL, 9 patients follicular lymphoma grade 3, 8 pts blastic mantle cell lymphoma, one patient aggressive marginal zone lymphoma and 11 patients peripheral T cell lymphoma. The median number of prior treatment regimens was 3 (range 1 to 6). 43 (72%) pts received at least one cycle of high-dose therapy and autologous SCT prior to alloSCT; 79% had early relapse (< 12 months) or primary progressive disease, 58% chemo-refractory disease and 52% had progressive disease with high or high intermediate age adjusted IPI immediately prior to conditioning. Allo-PBPC were obtained from HLA-identical siblings in 16 pts, from fully matched unrelated donors in 32 pts and from 1 locus mismatched unrelated donors in 12 pts. Engraftment of leukocytes was rapid (median 10 days, range 8–27) and all patients achieved complete (> 95%) donor type chimerism after alloSCT. Median observation time is 8 months (range 1–35 months). 32 pts died, in 20 patients death was attributed to treatment related causes. After one year, estimated overall survival is 47%, failure free survival is 43%, TRM is 37%, relapse rate is 33% and incidence of GVHD > grade 1 is 57%. With an observation time precluding final analysis, there are no significant differences between patients randomized to receive rituximab post transplant and those who were not. There was a trend to lower relapse rates in patients with GVHD > grade 1 (25% vs 44%, p=0.14). Intermediate intensity conditioning followed by allogeneic SCT is a valuable treatment option in patients with high-risk relapse of aggressive NHL. The basic incidence of GVHD and TRM is high. Due to the short observation time, a definitive conclusion regarding the impact of post transplant Rituximab cannot be drawn. The study will be continued.
Disclosure:Research Funding: Roche Pharma AG Deutschland for preclinical and clinical research. Honoraria Information: Roche Pharma AG Deutschland.