TY - JOUR
T1 - Nilotinib in steroid-refractory cGVHD
T2 - prospective parallel evaluation of response, according to NIH criteria and exploratory response criteria (GITMO criteria)
AU - Olivieri, A.
AU - Mancini, G.
AU - Olivieri, J.
AU - Marinelli Busilacchi, E.
AU - Cimminiello, M.
AU - Pascale, S. P.
AU - Nuccorini, R.
AU - Patriarca, F.
AU - Corradini, P.
AU - Bacigalupo, A.
AU - Angelini, S.
AU - Poloni, A.
AU - Grillo, G.
AU - Onida, F.
AU - Martino, M.
AU - Di Renzo, N.
AU - Nagler, A.
AU - Mordini, N.
AU - Bruno, B.
AU - Ciceri, F.
AU - Bonifazi, F.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85084126387&partnerID=8YFLogxK
U2 - 10.1038/s41409-020-0902-9
DO - 10.1038/s41409-020-0902-9
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C2 - 32332918
AN - SCOPUS:85084126387
VL - 55
SP - 2077
EP - 2086
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 11
ER -