Nilotinib in steroid-refractory cGVHD: prospective parallel evaluation of response, according to NIH criteria and exploratory response criteria (GITMO criteria).
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
12
11
2019
accepted:
03
04
2020
revised:
19
03
2020
pubmed:
26
4
2020
medline:
22
6
2021
entrez:
26
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32332918
doi: 10.1038/s41409-020-0902-9
pii: 10.1038/s41409-020-0902-9
doi:
Substances chimiques
Pyrimidines
0
Steroids
0
nilotinib
F41401512X
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2077-2086Références
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