SitemapContact Us
닫기
Search
Advanced Search +
닫기
Quick links
Most Cited Most Read Ahead of Print Archives Go to E-submission

Original Article

Split Viewer

Blood Res 2022; 57(2):

Published online June 30, 2022

https://doi.org/10.5045/br.2022.2021137

© The Korean Society of Hematology

Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea

Seo-Yeon Ahn1#, Sang Kyun Son2, Gyu Hyung Lee3, Inho Kim4, June-Won Cheong5, Won Sik Lee6, Byung Soo Kim7, Deog-Yeon Jo8, Chul Won Jung9, Chu Myoung Seong10, Jae Hoon Lee11, Young Jin Yuh12, Min Kyoung Kim13, Hun-Mo Ryoo14, Moo-Rim Park15, Su-Hee Cho16, Hoon-Gu Kim17, Dae Young Zang18, Jinny Park11, Hawk Kim11, Seryeon Lee19, Sung-Hyun Kim20, Myung Hee Chang21, Ho Sup Lee22, Chul Won Choi23, Jihyun Kwon24, Sung-Nam Lim25, Suk-Joong Oh26, Inkyung Joo27#, Dong-Wook Kim28#

Author Info. +

Department of Hematology-Oncology, 1Chonnam National University Hwasun Hospital, Hwasun, 2School of Medicine, Kyungpook National University, Daegu, Department of Internal Medicine, 3University of Ulsan College of Medicine, Asan Medical Center, 4Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, 5Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 6Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, 7Division of Hematology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Department of Internal Medicine, 8College of Medicine, Chungnam National Univeristy, Daejeon, 9Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 10Department of Hematology and Oncology, Ewha Womans University College of Medicine, Seoul, 11Division of Hematology, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Department of Internal Medicine, 12Inje University, Sanggye-Paik Hospital, Seoul, 13Yeungnam University College of Medicine, 14Division of Hematology-Oncology, Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, 15Department of Hematology-Oncology, Wonkwang University School of Medicine, Iksan, 16Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Department of Internal Medicine, 17Gyeongsang Institute of Health Sciences, Gyeongsang National University College of Medicine and Gyeongsang National University Changwon Hospital, Changwon, 18Hallym University Sacred Heart Hospital, Anyang, 19Korea University Ansan Hospital, Ansan, 20Dong-A University College of Medicine, Busan, Division of Oncology-Hematology, Department of Internal Medicine, 21National Health Insurance Service Ilsan Hospital, Goyang, 22Kosin University College of Medicine, Busan, Department of Internal Medicine, 23Korea University Guro Hospital, Seoul, 24Chungbuk National University College of Medicine, Cheongju, 25Inje University College of Medicine, Haeundae Paik Hospital, Busan, 26Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 27Novartis Korea Ltd., Seoul, 28Department of Hematology, Uijeongbu Eulji Medical Center, Leukemia Omics Research Institute, Eulji University Uijeongbu Campus, Uijeongbu, Korea

Correspondence to : Dong-Wook Kim, M.D., Ph.D.
Inkyung Joo, RPh.
Uijeongbu Eulji Medical Center, Leukemia Omics Research Institute, Eulji University Uijeongbu Campus, 712 Dongil-ro, Uijeongbu 11759, Korea (D.W.K.)
Novartis Korea Ltd., 49 Fl. Three IFC 10, Gukjegeumyung-ro, Yeongdeungpo-gu, Seoul 07326, Korea (I.J.)
E-mail: D.W.K., dwkim@eulji.ac.kr
I.J., inkyung.joo@novartis.com

#These authors contributed equally to this work.
*This study was supported by Novartis Korea as a regulatory, non-interventional, post-marketing surveillance study (study code: CAMN107CKR09).

Received: July 30, 2021; Revised: November 9, 2021; Accepted: May 4, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Go to

Background
Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea.
Methods
An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response.
Results
During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients).
Conclusion
This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

Keywords Nilotinib, Tyrosine kinase inhibitor, Chronic myeloid leukemia, Philadelphia chromosome positive, Post-marketing surveillance

Article

Original Article

Blood Res 2022; 57(2): 144-151

Published online June 30, 2022 https://doi.org/10.5045/br.2022.2021137

Copyright © The Korean Society of Hematology.

Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea

Seo-Yeon Ahn1#, Sang Kyun Son2, Gyu Hyung Lee3, Inho Kim4, June-Won Cheong5, Won Sik Lee6, Byung Soo Kim7, Deog-Yeon Jo8, Chul Won Jung9, Chu Myoung Seong10, Jae Hoon Lee11, Young Jin Yuh12, Min Kyoung Kim13, Hun-Mo Ryoo14, Moo-Rim Park15, Su-Hee Cho16, Hoon-Gu Kim17, Dae Young Zang18, Jinny Park11, Hawk Kim11, Seryeon Lee19, Sung-Hyun Kim20, Myung Hee Chang21, Ho Sup Lee22, Chul Won Choi23, Jihyun Kwon24, Sung-Nam Lim25, Suk-Joong Oh26, Inkyung Joo27#, Dong-Wook Kim28#

Department of Hematology-Oncology, 1Chonnam National University Hwasun Hospital, Hwasun, 2School of Medicine, Kyungpook National University, Daegu, Department of Internal Medicine, 3University of Ulsan College of Medicine, Asan Medical Center, 4Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, 5Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 6Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, 7Division of Hematology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Department of Internal Medicine, 8College of Medicine, Chungnam National Univeristy, Daejeon, 9Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 10Department of Hematology and Oncology, Ewha Womans University College of Medicine, Seoul, 11Division of Hematology, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Department of Internal Medicine, 12Inje University, Sanggye-Paik Hospital, Seoul, 13Yeungnam University College of Medicine, 14Division of Hematology-Oncology, Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, 15Department of Hematology-Oncology, Wonkwang University School of Medicine, Iksan, 16Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Department of Internal Medicine, 17Gyeongsang Institute of Health Sciences, Gyeongsang National University College of Medicine and Gyeongsang National University Changwon Hospital, Changwon, 18Hallym University Sacred Heart Hospital, Anyang, 19Korea University Ansan Hospital, Ansan, 20Dong-A University College of Medicine, Busan, Division of Oncology-Hematology, Department of Internal Medicine, 21National Health Insurance Service Ilsan Hospital, Goyang, 22Kosin University College of Medicine, Busan, Department of Internal Medicine, 23Korea University Guro Hospital, Seoul, 24Chungbuk National University College of Medicine, Cheongju, 25Inje University College of Medicine, Haeundae Paik Hospital, Busan, 26Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 27Novartis Korea Ltd., Seoul, 28Department of Hematology, Uijeongbu Eulji Medical Center, Leukemia Omics Research Institute, Eulji University Uijeongbu Campus, Uijeongbu, Korea

Correspondence to:Dong-Wook Kim, M.D., Ph.D.
Inkyung Joo, RPh.
Uijeongbu Eulji Medical Center, Leukemia Omics Research Institute, Eulji University Uijeongbu Campus, 712 Dongil-ro, Uijeongbu 11759, Korea (D.W.K.)
Novartis Korea Ltd., 49 Fl. Three IFC 10, Gukjegeumyung-ro, Yeongdeungpo-gu, Seoul 07326, Korea (I.J.)
E-mail: D.W.K., dwkim@eulji.ac.kr
I.J., inkyung.joo@novartis.com

#These authors contributed equally to this work.
*This study was supported by Novartis Korea as a regulatory, non-interventional, post-marketing surveillance study (study code: CAMN107CKR09).

Received: July 30, 2021; Revised: November 9, 2021; Accepted: May 4, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea.
Methods
An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response.
Results
During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients).
Conclusion
This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

Keywords: Nilotinib, Tyrosine kinase inhibitor, Chronic myeloid leukemia, Philadelphia chromosome positive, Post-marketing surveillance

Fig 1.

Download
Figure 1.Study flow chart.Abbreviation: CBC, complete blood count.
Blood Research 2022; 57: 144-151https://doi.org/10.5045/br.2022.2021137

Fig 2.

Download
Figure 2.Distribution of AE incidence by diagnosis.Abbreviations: AE, adverse events; AP, accelerated phase; CP, chronic phase.
Blood Research 2022; 57: 144-151https://doi.org/10.5045/br.2022.2021137

Fig 3.

Download
Figure 3.The incidence of adverse events (AEs) by categories. (A) AEs have been classified and evaluated along five severity categories: mild, moderate, severe, life threatening consequences, and death. (B) Action taken due to AEs has been evaluated along six categories as: none, permanent discontinuation, temporary discontinuation, dose reduction, dose escalation, and not applicable. (C) The incidence of AEs by sex. (D) The incidence of AEs by age.
Blood Research 2022; 57: 144-151https://doi.org/10.5045/br.2022.2021137

Table 1 . Demographics of patients..

Total (N=669)
Sex, N (%)
Male398 (59.5)
Female271 (40.5)
Age, years51.4±15.3
<40 yr (N, %)152 (22.7)
40–49 yr132 (19.7)
50–59 yr161 (24.1)
>60 yr224 (33.5)
Disease duration, mo1.6±5.4
Height, cm164.6±9.2
Weight, kg62.7±11.0
Line of treatment, N (%)
1st line328 (49.0)
2nd line341 (51.0)
Resistance
CP149 (22.3)
AP11 (1.6)
Intolerance
CP168 (25.1)
AP13 (1.9)

The continuous variables are presented as mean±SD. The categorical variables are presented as percentage..

Abbreviations: AP, accelerated phase; CP, chronic phase..

Table 2 . Adverse events and adverse drug reactions..

AEsADRs
Incidence, N (%)EventsIncidence, N (%)Events
Skin and subcutaneous tissue disorders149 (22.3)173115 (17.2)135
Rash82 (12.3)8674 (11.1)78
Pruritus41 (6.1)4229 (4.3)29
Alopecia8 (1.2)86 (0.9)6
Gastrointestinal disorders89 (13.3)12347 (7.0)61
Nausea17 (2.5)1913 (1.9)15
Dyspepsia15 (2.2)156 (0.9)6
Constipation14 (2.1)147 (1.0)7
Abdominal pain12 (1.8)126 (0.9)6
Abdominal pain upper10 (1.5)114 (0.6)5
Diarrhea8 (1.2)94 (0.6)4
Investigations75 (11.2)12651 (7.6)88
Alanine aminotransferase increased35 (5.2)3525 (3.7)25
Aspartate aminotransferase increased25 (3.7)2617 (2.5)18
Blood bilirubin increased16 (2.4)1610 (1.5)10
Platelet count decreased13 (1.9)1410 (1.5)11
Lipase increased7 (1.0)77 (1.0)7
Weight decreased7 (1.0)74 (0.6)4
Musculoskeletal and connective tissue disorders76 (11.4)8241 (6.1)46
Myalgia40 (6.0)4227 (4.0)29
Back pain9 (1.3)93 (0.4)3
Pain in extremity7 (1.0)74 (0.6)4
Infections and infestations62 (9.3)667 (1.0)7
Upper respiratory tract infection33 (4.9)342 (0.3)2
Nasopharyngitis8 (1.2)80 (0.0)0
Blood and lymphatic system disorders59 (8.8)8051 (7.6)69
Thrombocytopenia35 (5.2)3832 (4.8)35
Neutropenia20 (3.0)2019 (2.8)19
Anemia8 (1.2)105 (0.7)5
Nervous system disorders59 (8.8)6441 (6.1)43
Headache44 (6.6)4434 (5.1)34
Dizziness9 (1.3)94 (0.6)4
General disorders and administration site conditions50 (7.5)5730 (4.5)32
Fatigue15 (2.2)1513 (1.9)13
Pyrexia11 (1.6)113 (0.4)3
Metabolism and nutrition disorders38 (5.7)4516 (2.4)17
Decreased appetite12 (1.8)137 (1.0)8
Hyperglycemia8 (1.2)83 (0.4)3
Hypocalcemia7 (1.0)83 (0.4)3
Hepatobiliary disorders29 (4.3)3125 (3.7)27
Hyperbilirubinemia21 (3.1)2121 (3.1)21
Eye disorders27 (4.0)2911 (1.6)12
Dry eye8 (1.2)84 (0.6)4
Respiratory, thoracic, and mediastinal disorders25 (3.7)339 (1.3)9
Cough8 (1.2)81 (0.1)1
Dyspnea7 (1.0)83 (0.4)3
Psychiatric disorders11 (1.6)141 (0.1)1
Insomnia8 (1.2)81 (0.1)1
Total410 (61.3)973271 (40.5)559

Data presented only occurred 1.0% or more in AEs based on PT. Incidence (%): N/(N of safety evaluation patients)×100. Coding dictionary: MedDRA 19.1..

Abbreviations: ADRs, adverse drug reactions; AEs, adverse events; PT, preferred term..

Table 3 . Serious adverse events and serious adverse drug reactions..

SAEsSADRs
Incidence, N (%)EventsIncidence, N (%)Events
Skin and subcutaneous tissue disorders2 (0.3)21 (0.1)1
Rash1 (0.1)11 (0.1)1
Swelling face1 (0.1)10 (0.0)0
Gastrointestinal disorders5 (0.7)51 (0.1)1
Abdominal pain upper1 (0.1)10 (0.0)0
Gastritis1 (0.1)10 (0.0)0
Chronic gastritis1 (0.1)11 (0.1)1
Gastric hemorrhage1 (0.1)10 (0.0)0
Mechanical ileus1 (0.1)10 (0.0)0
Musculoskeletal and connective tissue disorders1 (0.1)10 (0.0)0
Fracture nonunion1 (0.1)10 (0.0)0
Infections and infestations5 (0.7)50 (0.0)0
Atypical pneumonia1 (0.1)10 (0.0)0
Infectious colitis1 (0.1)10 (0.0)0
Pharyngitis1 (0.1)10 (0.0)0
Pseudomembranous colitis1 (0.1)10 (0.0)0
Urinary tract infection1 (0.1)10 (0.0)0
Blood and lymphatic system disorders2 (0.3)31 (0.1)2
Thrombocytopenia1 (0.1)11 (0.1)1
Neutropenia1 (0.1)11 (0.1)1
Lymphadenitis1 (0.1)10 (0.0)0
Nervous system disorders4 (0.6)42 (0.3)2
Headache2 (0.3)21 (0.1)1
Cerebral artery occlusion1 (0.1)11 (0.1)1
Thalamic infarction1 (0.1)10 (0.0)0
General disorders and administration site conditions3 (0.4)41 (0.1)2
Pyrexia2 (0.3)20 (0.0)0
Asthenia1 (0.1)21 (0.1)2
Hepatobiliary disorders1 (0.1)10 (0.0)0
Cholecystitis chronic1 (0.1)10 (0.0)0
Respiratory, thoracic, and mediastinal disorders1 (0.1)10 (0.0)0
Pleural effusion1 (0.1)10 (0.0)0
Cardiac disorders3 (0.4)30 (0.0)0
Palpitations1 (0.1)10 (0.0)0
Angina unstable1 (0.1)10 (0.0)0
Cardiac failure congestive1 (0.1)10 (0.0)0
Renal and urinary disorders3 (0.4)40 (0.0)0
Acute kidney injury1 (0.1)10 (0.0)0
Renal disorder1 (0.1)10 (0.0)0
Tubulointerstitial nephritis1 (0.1)10 (0.0)0
Ureteral disorder1 (0.1)10 (0.0)0
Injury, poisoning, and procedural complications1 (0.1)10 (0.0)0
Foot fracture1 (0.1)10 (0.0)0
Neoplasms benign, malignant, and unspecified (incl cysts and polyps)2 (0.3)20 (0.0)0
Malignant neoplasm progression1 (0.1)10 (0.0)0
Malignant palate neoplasm1 (0.1)10 (0.0)0
Product issues1 (0.1)10 (0.0)0
Device dislocation1 (0.1)10 (0.0)0
Total30 (4.5)375 (0.7)8

Incidence (%): N/(N of safety evaluation patients)×100. Coding dictionary: MedDRA 19.1..

Abbreviations: SADRs, serious adverse drug reactions; SAEs, serious adverse events..
Blood Res
Volume 59 2024
Current Issue Archives

Stats or Metrics

Share this article on

  • line

Related articles in BR

Blood Research

pISSN 2287-979X
eISSN 2288-0011
qr-code Download