Ching-Yuan Kuo1, Po-Nan Wang2, Wen-Li Hwang3, Cheng-Hwai Tzeng4, Li-Yaun Bai5, Jih-Luh Tang6, Ming-Chih Chang7, Sheng-Fung Lin8, Tsai-Yun Chen9, Yeu-Chin Chen10, Tran-Der Tan11, Chih-Yi Hsieh12, Chinjune Lin13, Clinton Lai14, Darko Miljkovic15, Cheng-Shyong Chang16. 1. Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan. 2. Chang Gung Memorial Hospital-Linko, Taoyuan, Taiwan. 3. Taichung Veterans General Hospital, Taichung City, Taiwan. 4. Taipei Veterans General Hospital, Taipei, Taiwan. 5. China Medical University Hospital, Taichung, Taiwan. 6. National Taiwan University Hospital, Taipei, Taiwan. 7. Mackay Memorial Hospital, Taipei, Taiwan. 8. Kaohsiung Medical University and Hospital, Kaohsiung, Taiwan. 9. National Cheng Kung University Hospital, Tainan, Taiwan. 10. Tri-Service General Hospital (TSGH), Taipei, Taiwan. 11. Koo Foundation Sun Yet-Sen Cancer Center, Taipei, Taiwan. 12. Novartis (Taiwan) Co. Ltd., Taipei, Taiwan. 13. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. 14. Novartis Asia Pacific Pharmaceuticals Pte. Ltd., Singapore. 15. Novartis Pharma AG, Basel, Switzerland. 16. Changhua Christian Hospital, No. 135, Nan-Xiao Street, Changhua, 500 Taiwan.
Abstract
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-ABL1IS ⩽0.01%) and MR4.5 (BCR-ABL1IS ⩽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.
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-ABL1IS ⩽0.01%) and MR4.5 (BCR-ABL1IS ⩽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.
Authors: A de Klein; A G van Kessel; G Grosveld; C R Bartram; A Hagemeijer; D Bootsma; N K Spurr; N Heisterkamp; J Groffen; J R Stephenson Journal: Nature Date: 1982-12-23 Impact factor: 49.962
Authors: Giuseppe Saglio; Dong-Wook Kim; Surapol Issaragrisil; Philipp le Coutre; Gabriel Etienne; Clarisse Lobo; Ricardo Pasquini; Richard E Clark; Andreas Hochhaus; Timothy P Hughes; Neil Gallagher; Albert Hoenekopp; Mei Dong; Ariful Haque; Richard A Larson; Hagop M Kantarjian Journal: N Engl J Med Date: 2010-06-05 Impact factor: 91.245
Authors: Hagop M Kantarjian; Francis J Giles; Kapil N Bhalla; Javier Pinilla-Ibarz; Richard A Larson; Norbert Gattermann; Oliver G Ottmann; Andreas Hochhaus; Jerald P Radich; Giuseppe Saglio; Timothy P Hughes; Giovanni Martinelli; Dong-Wook Kim; Yaping Shou; Neil J Gallagher; Rick Blakesley; Michele Baccarani; Jorge Cortes; Philipp D le Coutre Journal: Blood Date: 2010-11-22 Impact factor: 22.113
Authors: Michele Baccarani; Jorge Cortes; Fabrizio Pane; Dietger Niederwieser; Giuseppe Saglio; Jane Apperley; Francisco Cervantes; Michael Deininger; Alois Gratwohl; François Guilhot; Andreas Hochhaus; Mary Horowitz; Timothy Hughes; Hagop Kantarjian; Richard Larson; Jerald Radich; Bengt Simonsson; Richard T Silver; John Goldman; Rudiger Hehlmann Journal: J Clin Oncol Date: 2009-11-02 Impact factor: 44.544
Authors: F J Giles; P D le Coutre; J Pinilla-Ibarz; R A Larson; N Gattermann; O G Ottmann; A Hochhaus; J P Radich; G Saglio; T P Hughes; G Martinelli; D-W Kim; S Novick; K Gillis; X Fan; J Cortes; M Baccarani; H M Kantarjian Journal: Leukemia Date: 2012-07-05 Impact factor: 11.528
Authors: Timothy Hughes; Giuseppe Saglio; Susan Branford; Simona Soverini; Dong-Wook Kim; Martin C Müller; Giovanni Martinelli; Jorge Cortes; Lan Beppu; Enrico Gottardi; Dongho Kim; Philipp Erben; Yaping Shou; Ariful Haque; Neil Gallagher; Jerald Radich; Andreas Hochhaus Journal: J Clin Oncol Date: 2009-08-03 Impact factor: 44.544
Authors: Susan Branford; Dong-Wook Kim; Simona Soverini; Ariful Haque; Yaping Shou; Richard C Woodman; Hagop M Kantarjian; Giovanni Martinelli; Jerald P Radich; Giuseppe Saglio; Andreas Hochhaus; Timothy P Hughes; Martin C Müller Journal: J Clin Oncol Date: 2012-10-29 Impact factor: 44.544
Authors: Timothy P Hughes; Jeffrey H Lipton; Nelson Spector; Francisco Cervantes; Ricardo Pasquini; Nelma Cristina D Clementino; Pedro Enrique Dorlhiac Llacer; Anthony P Schwarer; Francois-Xavier Mahon; Delphine Rea; Susan Branford; Das Purkayastha; LaTonya Collins; Tomasz Szczudlo; Brian Leber Journal: Blood Date: 2014-06-19 Impact factor: 22.113