Bone Marrow Transplantation https://doi.org/10.1038/s41409-020-0902-9 ARTICLE Nilotinib in steroid-refractory cGVHD: prospective parallel evaluation of response, according to NIH criteria and exploratory response criteria (GITMO criteria) A. Olivieri 1,2 ● G. Mancini 1 ● J. Olivieri 3 ● E. Marinelli Busilacchi 2 ● M. Cimminiello 4 ● S. P. Pascale 4 ● R. Nuccorini 4 ● F. Patriarca 3 ● P. Corradini 5 ● A. Bacigalupo 6 ● S. Angelini 7 ● A. Poloni 1,2 ● G. Grillo 8 ● F. Onida 9 ● M. Martino 10 ● N. Di Renzo 11 ● A. Nagler 12 ● N. Mordini 13 ● B. Bruno 14 ● F. Ciceri 15 ● F. Bonifazi 16 Received: 12 November 2019 / Revised: 19 March 2020 / Accepted: 3 April 2020 © The Author(s), under exclusive licence to Springer Nature Limited 2020 Abstract 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. * A. Olivieri a.olivieri@univpm.it 1 Unit of Hematology, AUO Ospedali Riuniti di Ancona, Ancona, Italy 2 Department of Clinical and Molecular Science, Università Politecnica delle Marche, Ancona, Italy 3 Department of Hematology, Centro Trapianti e Terapie Cellulari, Azienda Sanitaria Universitaria Integrata, Udine, Italy 4 Regional Department of Hematology, U.O.C. of Hematology and Stem Cell Transplantation, Azienda Ospedaliera Regionale San Carlo, Potenza, Italy 5 Department of Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy 6 Department of Hematology, Fondazione Policlinico Universitario Gemelli IRCCS, Universita’ Cattolica del Sacro Cuore, Roma, Italy 7 U.O.C of Hematology, Ospedale C.G. Mazzoni, Ascoli Piceno, Italy 8 Division of Hematology and Oncology, ASST Grande Ospedale Metropolitano Niguarda Milan, Milan, Italy 9 BMT Center, Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy 10 Stem Cell Transplantation Unit (CTMO), Department of Hemato- Oncology and Radiotherapy, Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, Reggio Calabria, Italy 11 Haematology and BMT Unit, Ospedale Vito Fazzi, Lecce, Italy 12 Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Tel Aviv University, Tel Aviv, Israel 13 BMT Center, Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy 14 S.S.D. Allogenic Stem Cell Transplantation, Department of Oncology, Presidio Molinette, AOU Città della Salute e della Scienza di Torino, Torino, Italy 15 IRCCS San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Milano, Italy 16 Institute of Hematology, “Seragnoli” University Hospital S. Orsola-Malpighi, Bologna, Italy Supplementary information The online version of this article (https:// doi.org/10.1038/s41409-020-0902-9) contains supplementary material, which is available to authorized users. 1234567890();,: 1234567890();,: