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.
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/m(2). 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.
Stanford University Medical Center, Stanford, California.
Ginna G
GG
Laport
The EMMES Corporation, Rockville, Maryland.
Juan
J
Wu
Medical College of Wisconsin, Milwaukee, Wisconsin.
Brent
B
Logan
University of Minnesota, Minneapolis, Minnesota.
Veronika
V
Bachanova
University of Texas/MD Anderson Cancer Center, Houston, Texas.
Chitra
C
Hosing
Medical College of Wisconsin, Milwaukee, Wisconsin.
Timothy
T
Fenske
University of Wisconsin, Madison, Wisconsin.
Walter
W
Longo
Ohio State/Arthur G. James Cancer Hospital, Columbus, Ohio.
Steven M
SM
Devine
City of Hope National Medical Center, Duarte, California.
Auayporn
A
Nademanee
The EMMES Corporation, Rockville, Maryland.
Iris
I
Gersten
Medical College of Wisconsin, Milwaukee, Wisconsin.
Mary
M
Horowitz
University Hospitals of Cleveland/Case Western, Cleveland, Ohio.
Hillard M
HM
Lazarus
Division of Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina. Electronic address: marcie_riches@med.unc.edu.
Marcie L
ML
Riches
D000328:Adult; D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008224:Lymphoma, Follicular / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage; D016879:Salvage Therapy / Q000379:methods / Q000401:mortality; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000074322:Antineoplastic Agents, Immunological; D019653:Myeloablative Agonists; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
Allogeneic transplantation; Clinical trial; Follicular lymphoma; Reduced intensity