A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after non-myeloablative unrelated donor transplantation
Brian Kornblit,
David G. Maloney,
Barry E. Storer,
Michael B. Maris,
Lars Vindeløv,
Parameswaran Hari,
Amelia A. Langston,
Michael A. Pulsipher,
Wolfgang A. Bethge,
Thomas R. Chauncey,
Thoralf Lange,
Finn B. Petersen,
Kai Hübel,
Ann E. Woolfrey,
Mary E.D. Flowers,
Rainer Storb,
Brenda M. Sandmaier
Affiliations
Brian Kornblit
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
David G. Maloney
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
Barry E. Storer
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Department of Biostatistics, University of Washington, Seattle, WA, USA
Michael B. Maris
Colorado Blood Cancer Institute, Denver, CO, USA
Lars Vindeløv
Rigshospitalet, University of Copenhagen, Denmark
Parameswaran Hari
Medical College of Wisconsin, Milwaukee, WI, USA
Amelia A. Langston
Emory University, Atlanta, GA, USA
Michael A. Pulsipher
Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA
Wolfgang A. Bethge
University of Tübingen Medical Center, Germany
Thomas R. Chauncey
VA Puget Sound Health Care System, Seattle, WA, USA
Thoralf Lange
University of Leipzig, Germany
Finn B. Petersen
LDS Hospital, Salt Lake City, UT, USA
Kai Hübel
University of Cologne, Germany
Ann E. Woolfrey
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
Mary E.D. Flowers
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
Rainer Storb
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
Brenda M. Sandmaier
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
The study is a randomized phase II trial investigating graft-versus-host disease prophylaxis after non-myeloablative (90 mg/m2 fludarabine and 2 Gy total body irradiation) human leukocyte antigen matched unrelated donor transplantation. Patients were randomized as follows: arm 1 – tacrolimus 180 days and mycophenolate mofetil 95 days (n=69); arm 2 – tacrolimus 150 days and mycophenolate mofetil 180 days (n=71); arm 3 – tacrolimus 150 days, mycophenolate mofetil 180 days and sirolimus 80 days (n=68). All patients had sustained engraftment. Grade II-IV acute graft-versus-host disease rates in the 3 arms were 64%, 48% and 47% at Day 150, respectively (arm 3 vs. arm 1 (hazard ratio 0.62; P=0.04). Owing to the decreased incidence of acute graft-versus-host disease, systemic steroid use was lower at Day 150 in arm 3 (32% vs. 55% in arm 1 and 49% in arm 2; overall P=0.009 by hazard ratio analysis). The Day 150 incidence of cytomegalovirus reactivation was lower in arm 3 (arm 1, 54%; arm 2, 47%; arm 3, 22%; overall P=0.002 by hazard ratio analysis). Non-relapse mortality was comparable in the three arms at two years (arm 1, 26%; arm 2, 23%; arm 3, 18%). Toxicity rates and other outcome measures were similar between the three arms. The addition of sirolimus to tacrolimus and mycophenolate mofetil is safe and associated with lower incidence of acute graft-versus-host disease and cytomegalovirus reactivation. (clinicaltrials.gov identifier: 00105001).
