Reduced Intensity Conditioning (RIC) with Rituximab Yields Excellent Outcomes after Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Relapsed Follicuar Lymphoma (FL): A Phase II Multicenter Trial from the Blood and Marrow Transplant Network (BMT CTN 0701)

Allogeneic HCT has been shown to induce long term remissions in FL pts who have chemosensitive relapsed disease. The BMT CTN (sponsored by the NHLBI and NCI) conducted a multicenter phase 2 trial to examine the efficacy of rituximab (RTX)-containing RIC alloHCT (BMT CTN 0701: NCT 00912223). The primary objective was 2 year progression-free survival (PFS). Conditioning regimen consisted of fludarabine, cyclophosphamide and high-dose RTX (FCR) in which three* of the 4 doses of RTX were given IV at a dose of 1000 mg/m² on days -13, -6*, + 1* and +8*. Graft vs host disease (GvHD) prophylaxis consisted of tacrolimus and mini-methotrexate. Sixty five patients who demonstrated chemosensitivity to the most recent salvage regimen were enrolled from 2009 to 2012 and 62 were evaluable. Median age was 55 years (range, 29-74). Matched related (47%) and unrelated (53%) donors provided mobilized blood allografts. This group was heavily pre-treated as 77% of pts received ≥ 3 prior regimens with 32% having received ≥ 5 prior regimens. No graft failures occurred and the overall response rate after HCT was 94% with 90% achieving a complete remission (CR), including 24 patients not in CR before alloHCT. With a median follow-up of 24 months (range, 12-31), the 2 year PFS and overall survival were 75% (95% confidence interval: 61%, 84%) and 83% (95% confidence interval: 70%, 90%) respectively. The 2 year cumulative incidence of relapse/progression and non-relapse mortality was 10% and 15%, respectively. The 2 year cumulative incidences of grade 2-4 and grade 3-4 acute GvHD were 27% and 10%, respectively, with a 55% incidence of extensive chronic GvHD. Of the 10 reported deaths, 1 was from relapse/progression, 6 were related to GvHD, 2 were related to infections and 1 unexpected death. Serum RTX concentrations were examined at 4 time points up to 1 year. Serum RTX levels peaked at day +28 and remained detectable as late as 1 year in 23 pts with available 1-year RTX level results (n=39). Blood absolute T lymphocytes including CD4 and CD8 subsets remained within normal range up to 1 year post-HCT; however, B-cell lymphocytes were significantly reduced or not detectable up to 1 year post-HCT. In conclusion, RIC allogeneic HCT with the FCR conditioning regimen confers high CR rates, a low incidence of relapse/progression and notable survival incidences in heavily pretreated FL patients. Serum RTX levels were detected in a majority of the patients for up to 1 yr post-HCT which may have contributed to the low incidence of relapse/progression.

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