We conducted a phase I–II study to evaluate Nilotinib (NIL) safety and pharmacokinetics in 22 SR-cGVHD patients; we also evaluated ORR by using in parallel NIH criteria and an exploratory approach, combining objective improvement (OI) without failure criteria (GITMO criteria). Results: 22 patients were enrolled. After dose escalation up to 600 mg/day, MTD was not reached. Main toxicities were asthenia, headache, nausea, pruritus, cramps, and mild anemia. Mean and median plasma concentrations of NIL (C-NIL) were 817 (SD ± 450) and 773 ng/ml. ORR at 6 months, according to 2005 and 2014 NIH and GITMO criteria were 27.8%, 22.2%, and 55.6% respectively; close correspondence has been observed for ORR, according to 2014 NIH criteria, both assessed in a conventional way and assisted by dedicated software (CROSY). At 48 months OS was 75% while FFS, according to NIH and GITMO criteria, was 30 and 25%. In conclusion the safety profile of NIL and long-term outcome makes NIL an attractive option in SR-cGVHD. Exploratory GITMO criteria could represent an alternative tool for easy response evaluation in patients with prevalent skin and lung involvement, but require validation in a larger population; CROSY software showed excellent reliability in capturing ORR according to the 2014 NIH criteria.
Nilotinib in steroid-refractory cGVHD: prospective parallel evaluation of response, according to NIH criteria and exploratory response criteria (GITMO criteria) / Olivieri, A.; Mancini, G.; Olivieri, J.; Marinelli Busilacchi, E.; Cimminiello, M.; Pascale, S. P.; Nuccorini, R.; Patriarca, F.; Corradini, P.; Bacigalupo, A.; Angelini, S.; Poloni, A.; Grillo, G.; Onida, F.; Martino, M.; Di Renzo, N.; Nagler, A.; Mordini, N.; Bruno, B.; Ciceri, F.; Bonifazi, F.. - In: BONE MARROW TRANSPLANTATION. - ISSN 0268-3369. - 55:11(2020), pp. 2077-2086. [10.1038/s41409-020-0902-9]