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

• Published in: Haematologica (Roma) Vol. 103; no. 11; pp. 1915 - 1924
• Main Authors: Carpenter, Paul A., Logan, Brent R., Lee, Stephanie J., Weisdorf, Daniel J., Johnston, Laura, Costa, Luciano J., Kitko, Carrie L., Bolaños-Meade, Javier, Sarantopoulos, Stefanie, Alousi, Amin M., Abhyankar, Sunil, Waller, Edmund K., Mendizabal, Adam, Zhu, Jiaxi, O’Brien, Kelly A., Lazaryan, Aleksandr, Wu, Juan, Nemecek, Eneida R., Pavletic, Steven Z., Cutler, Corey S., Horowitz, Mary M., Arora, Mukta
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.11.2018
• Subjects: Aged; Calcineurin Inhibitors - administration & dosage; Chronic Disease; Disease-Free Survival; Female; Graft vs Host Disease - mortality; Graft vs Host Disease - therapy; Humans; Male; Middle Aged; Photopheresis; Prednisolone - administration & dosage; Sirolimus - administration & dosage; Survival Rate
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2018.195123

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.