Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia.
Patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. A total of 119 patients were enrolled and had a median duration of treatment of 202 days (range, 2-611 days). An HR was observed in 56 patients (47%; 95% confidence interval [CI], 38%-56%). Major cytogenetic response (MCyR) was observed in 35 patients (29%; 95% CI, 21%-39%). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79% (95% CI, 70%-87%). Nonhematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common grade 3 or higher hematologic adverse events were thrombocytopenia (35%) and neutropenia (21%). Grade 3 or higher bilirubin and lipase elevations occurred in 9% and 18% of patients, respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials.gov as NCT00384228.
le Coutre
Philipp
P
Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Germany. philipp.lecoutre@charite.de
Ottmann
Oliver G
OG
Giles
Francis
F
Kim
Dong-Wook
DW
Cortes
Jorge
J
Gattermann
Norbert
N
Apperley
Jane F
JF
Larson
Richard A
RA
Abruzzese
Elisabetta
E
O'Brien
Stephen G
SG
Kuliczkowski
Kazimierz
K
Hochhaus
Andreas
A
Mahon
Francois-Xavier
FX
Saglio
Giuseppe
G
Gobbi
Marco
M
Kwong
Yok-Lam
YL
Baccarani
Michele
M
Hughes
Timothy
T
Martinelli
Giovanni
G
Radich
Jerald P
JP
Zheng
Ming
M
Shou
Yaping
Y
Kantarjian
Hagop
H
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001772:Blood Cell Count; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D000068877:Imatinib Mesylate; D015465:Leukemia, Myeloid, Accelerated Phase / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use* / Q000633:toxicity; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D012449:Safety
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib