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.

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.

Publisher Copyright:
© 2016 American Society for Blood and Marrow Transplantation

Keywords

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

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