Safety and efficacy of nilotinib in routine clinical practice in patients with chronic myeloid leukemia in chronic or accelerated phase with resistance or intolerance to imatinib: results from the NOVEL study.

Autor: Kuo CY; Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan., Wang PN; Chang Gung Memorial Hospital-Linko, Taoyuan, Taiwan., Hwang WL; Taichung Veterans General Hospital, Taichung City, Taiwan., Tzeng CH; Taipei Veterans General Hospital, Taipei, Taiwan., Bai LY; China Medical University Hospital, Taichung, Taiwan., Tang JL; National Taiwan University Hospital, Taipei, Taiwan., Chang MC; Mackay Memorial Hospital, Taipei, Taiwan., Lin SF; Kaohsiung Medical University and Hospital, Kaohsiung, Taiwan., Chen TY; National Cheng Kung University Hospital, Tainan, Taiwan., Chen YC; Tri-Service General Hospital (TSGH), Taipei, Taiwan., Tan TD; Koo Foundation Sun Yet-Sen Cancer Center, Taipei, Taiwan., Hsieh CY; Novartis (Taiwan) Co. Ltd., Taipei, Taiwan., Lin C; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Lai C; Novartis Asia Pacific Pharmaceuticals Pte. Ltd., Singapore., Miljkovic D; Novartis Pharma AG, Basel, Switzerland., Chang CS; Changhua Christian Hospital, No. 135, Nan-Xiao Street, Changhua, 500 Taiwan.
Jazyk: angličtina
Zdroj: Therapeutic advances in hematology [Ther Adv Hematol] 2018 Mar; Vol. 9 (3), pp. 65-78. Date of Electronic Publication: 2018 Mar 04.
DOI: 10.1177/2040620718756603
Abstrakt: Background: Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), is approved for the treatment of patients with chronic myeloid leukemia (CML) in many countries, including Taiwan. Though a number of controlled clinical trials have demonstrated the safety and efficacy of nilotinib, studies assessing the safety and efficacy of nilotinib in routine clinical practice are limited.
Methods: The current study was an open-label, single-arm study conducted across 12 centers in Taiwan in adult patients with CML in chronic or accelerated phase with confirmed Ph+ chromosome (or BCR-ABL) and resistant or intolerant to one or more previous TKIs. The primary objective was to collect the long-term safety data in patients treated with nilotinib 400 mg, twice daily for up to 2 years.
Results: The study enrolled 85 patients with CML, including 76 in the chronic phase (CML-CP) and 9 in the accelerated phase (CML-AP). Overall, 1166 adverse events (AEs) were reported in 80 patients (94.1%), of which 70 AEs (6%) in 28 patients (32.9%) were serious and 336 AEs (28.8%) reported in 60 patients (70.6%) were drug-related. Common drug-related AEs were thrombocytopenia (21.2%), increased alanine aminotransferase (21.2%) and pruritus (17.7%). Of the 85 patients, 19 switched from imatinib due to intolerance - AEs were resolved in 16 of these 19 patients (84.2%). By 24 months, the cumulative rates of complete cytogenetic response (CCyR), major molecular response (MMR), MR4.0 ( BCR-ABL1 IS ⩽0.01%) and MR4.5 ( BCR-ABL1 IS ⩽0.0032%) were 75.3, 56.8, 16.2 and 7.4%, respectively. Patients with CML-CP at baseline had higher overall survival (OS) and progression-free survival (PFS) than those with CML-AP.
Conclusion: This is the first study that demonstrated that nilotinib is effective and well-tolerated in patients resistant or intolerant to imatinib in the real-world setting in Taiwan, reflecting effective management of CML by physicians under routine clinical practice in Taiwan.
Competing Interests: Conflict of interest statement: Ching-Yuan Kuo has received honoraria from Novartis, Roche, Celgene, Takeda and Janssen. Cheng-Shyong Chang has received fees for consulting from Novartis, Roche, Takeda, Celgene and Janssen, participated in a speakers’ bureau for Novartis, Janssen and Roche, and received honoraria from Novartis, Roche, Takeda, Celgene, Janssen, Kyrin and MSD. Chinjune Lin, Clinton Lai and Darko Miljkovic are employees of Novartis. Chih-Yi Hsieh was an employee of Novartis from January 2013 to June 2015. All other authors have no conflicts of interest to disclose.
Databáze: MEDLINE
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