A phase II/III randomized, multicenter trial of prednisone/sirolimus prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft--host disease: BMT CTN 0801.
2018 11
Journal Article
Authors:
Carpenter, P.A.;
Logan, B.R.;
Lee, S.J.;
Weisdorf, D.J.;
Johnston, L.;
Costa, L.J.;
Kitko, C.L.;
Bolaños-Meade, J.;
Sarantopoulos, S.;
Alousi, A.M.;
Abhyankar, S.;
Waller, E.K.;
Mendizabal, A.;
Zhu, J.;
O'Brien, K.A.;
Lazaryan, A.;
Wu, J.;
Nemecek, E.R.;
Pavletic, S.Z.;
Cutler, C.S.;
Horowitz, M.M.;
Arora, M.
Secondary:
Haematologica
Volume:
103
Pagination:
1915-1924
Issue:
11
PMID:
29954931
DOI:
10.3324/haematol.2018.195123
Keywords:
Aged; Calcineurin Inhibitors; chronic disease; Disease-Free Survival; Female; Graft vs Host Disease; Humans; Male; Middle Aged; Photopheresis; Prednisolone; sirolimus; Survival Rate
Abstract:
Initial therapy of chronic graft--host disease is prednisone ± a calcineurin-inhibitor, but most patients respond inadequately. In a randomized, 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--host disease in treatment-naïve or early inadequate responders. Primary endpoints of this study were proportions of subjects alive without relapse or secondary therapy with 6-month complete or partial response in phase II, or with 2-year complete response in phase III. The prednisone/sirolimus/photopheresis arm closed prematurely because of slow accrual and the remaining two-drug 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% 50.0%, =0.87), or 2-year complete response (14.7% 15.5%, =0.90). Serum creatinine values >1.5 times baseline were less frequent in the calcineurin-inhibitor-free arm at 2 months (1.5% 11.7%, =0.025) and 6 months (7.8% 24.0%, =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 (=0.02 and =0.04, respectively) and 6 months (=0.007 and =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% 46.2%, =0.78; 81.5% 74%, =0.28). Based on similar long-term outcomes, prednisone/sirolimus is a therapeutic alternative to prednisone/sirolimus/calcineurin-inhibitor for chronic graft--host disease, being easier to administer and better tolerated.
