Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and High-Dose Rituximab for Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma: A Phase Two Multicenter Trial from the Blood and Marrow Transplant Clinical Trials Network

for the Blood and Marrow Transplant Clinical Trials Network

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24 Scopus citations

Abstract

Allogeneic (allo) hematopoietic cell transplantation (HCT) can induce long-term remissions in chemosensitive relapsed follicular lymphoma (FL). The Blood and Marrow Transplant Clinical Trials Network conducted a multicenter phase 2 trial to examine the efficacy of alloHCT using reduced-intensity conditioning with rituximab (RTX) in multiply relapsed, chemosensitive FL. The primary endpoint was 2-year progression-free survival (PFS). The conditioning regimen consisted of fludarabine, cyclophosphamide, and high-dose RTX (FCR), in which 3 of the 4 doses of RTX were administered at a dose of 1 gm/m2. Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus and methotrexate. Sixty-five patients were enrolled and 62 were evaluable. Median age was 55 years (range, 29 to 74). This group was heavily pretreated: 77% had received ≥ 3 prior regimens, 32% had received ≥ 5 prior regimens, and 11% had received prior autologous HCT. Donors were HLA-matched siblings (n = 33) or HLA-matched unrelated adults (n = 29). No graft failures occurred. The overall response rate after HCT was 94% with 90% in complete remission (CR), including 24 patients not in CR before alloHCT. With a median follow-up of 47 months (range, 30 to 73), 3-year PFS and overall survival rates were 71% (95% confidence interval, 58% to 81%) and 82% (95% confidence interval, 70% to 90%), respectively. Three-year cumulative incidences of relapse/progression and nonrelapse mortality were 13% and 16%, respectively. Two-year cumulative incidences of grades 2 to 4 and grades 3 or 4 acute GVHD were 27% and 10%, respectively, and extensive chronic GVHD incidence was 55%. Serum RTX concentrations peaked at day +28 and remained detectable as late as 1 year in 59% of patients with available data. In conclusion, alloHCT with FCR conditioning confers high CR rates, a low incidence of relapse/progression, and excellent survival probabilities in heavily pretreated FL patients.

Original languageEnglish (US)
Pages (from-to)1440-1448
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number8
DOIs
StatePublished - Aug 1 2016

Bibliographical note

Funding Information:
This work was supported by the National Heart, Lung and Blood Institute and the National Cancer Institute through the National Institutes of Health Grant U10HL069294 ; Eastern Cooperative Oncology Group grants CA180820 , CA180853 , and CA 180799 ; and Southwest Oncology Group NCTN grant U10 CA180888 .

Funding Information:
Financial disclosure statement: Support for this study was provided by grant U10HL069294 from the National Heart, Lung and Blood Institute and the National Cancer Institute , along with contributions by Genentech, Inc. and funding by the Alliance for Clinical Trials in Oncology (grant nos. U10CA180821 and U10CA180882 ), the ECOG-ACRIN Cancer Research Group ( CA 180820 , CA 180853 , CA 180799 ) and Southwest Oncology Group ( U10CA180888 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the above-mentioned parties.

Keywords

  • Allogeneic transplantation
  • Clinical trial
  • Follicular lymphoma
  • Reduced intensity

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