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Stem Cell Transplantation
A phase II/III randomized, multicenter trial of prednisone/sirolimus versus prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft-versus-host disease:
BMT CTN 0801
Ferrata Storti Foundation
Paul A. Carpenter,1 Brent R. Logan,2 Stephanie J. Lee,1 Daniel J. Weisdorf,3 Laura Johnston,4 Luciano J. Costa,5 Carrie L. Kitko,6 Javier Bolaños-Meade,7 Stefanie Sarantopoulos,8 Amin M. Alousi,9 Sunil Abhyankar,10 Edmund K. Waller,11 Adam Mendizabal,12 Jiaxi Zhu,12 Kelly A. O’Brien,12 Aleksandr Lazaryan,3 Juan Wu,12 Eneida R. Nemecek,13 Steven Z. Pavletic,14 Corey S. Cutler,15 Mary M. Horowitz2 and Mukta Arora3 on behalf of the BMT CTN.
Haematologica 2018 Volume 103(11):1915-1924
1Fred Hutchinson Cancer Research Center, Seattle, WA; 2Medical College of Wisconsin, Milwaukee, WI; 3University of Minnesota, Minneapolis, MN; 4Stanford Hospital and Clinics, Stanford, CA; 5University of Alabama at Birmingham, AL; 6Vanderbilt University School of Medicine, Nashville, TN; 7Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; 8Duke University Medical Center, Durham, NC; 9University of Texas MD Anderson Cancer Center, Houston, TX; 10The University of Kansas Medical Center, Kansas City, KS; 11Emory University School of Medicine, Atlanta, GA; 12The Emmes Corporation, Rockville, MD; 13Oregon Health and Sciences University, Portland, OR; 14Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD and 15Dana Farber Cancer Institute, Boston, MA, USA
ABSTRACT
Initial therapy of chronic graft-versus-host disease is prednisone ± a cal- cineurin-inhibitor, but most patients respond inadequately. In a ran- domized, adaptive, phase II/III, multicenter trial we studied whether prednisone/sirolimus or prednisone/sirolimus/photopheresis was more effective than prednisone/sirolimus/calcineurin-inhibitor for treating chronic graft-versus-host disease in treatment-naïve or early inadequate responders. Primary endpoints of this study were proportions of sub- jects alive without relapse or secondary therapy with 6-month com- plete or partial response in phase II, or with 2-year complete response in phase III. The prednisone/sirolimus/photopheresis arm closed pre- maturely because of slow accrual and the remaining two-drug versus three-drug study ended in phase II due to statistical futility with 138 evaluable subjects. The two-drug and three-drug arms did not differ in rates of 6-month complete or partial response (48.6% versus 50.0%, P=0.87), or 2-year complete response (14.7% versus 15.5%, P=0.90). Serum creatinine values >1.5 times baseline were less frequent in the calcineurin-inhibitor-free arm at 2 months (1.5% versus 11.7%, P=0.025) and 6 months (7.8% versus 24.0%, P=0.016). Higher adjusted Short Form-36 Physical Component Summary and Physical Functioning scores were seen in the two-drug arm at both 2 months (P=0.02 and P=0.04, respectively) and 6 months (P=0.007 and P=0.001, respectively). Failure-free survival and overall survival rates at 2 years were similar for patients in the the two-drug and three-drug arms (48.6% versus 46.2%, P=0.78; 81.5% versus 74%, P=0.28). Based on sim- ilar long-term outcomes, prednisone/sirolimus is a therapeutic alterna- tive to prednisone/sirolimus/calcineurin-inhibitor for chronic graft-ver- sus-host disease, being easier to administer and better tolerated. Clinicaltrials.gov identifier: NCT01106833.
Correspondence:
pcarpent@fredhutch.org
Received: April 7, 2018. Accepted: June 26, 2018. Pre-published: June 28, 2018.
doi:10.3324/haematol.2018.195123
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/11/1915
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