title: Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study.
abstract: The aim of the Korean Imatinib Discontinuation Study was to identify predictors for safe and successful imatinib discontinuation. A total of 90 patients with a follow-up of ≥12 months were analyzed. After a median follow-up of 26.6 months after imatinib discontinuation, 37 patients lost the major molecular response. The probability of sustained major molecular response at 12 months and 24 months was 62.2% and 58.5%, respectively. All 37 patients who lost major molecular response were retreated with imatinib therapy for a median of 16.9 months, and all achieved major molecular response again at a median of 3.9 months after resuming imatinib therapy. We observed newly developed or worsened musculoskeletal pain and pruritus in 27 (30%) patients after imatinib discontinuation. Imatinib withdrawal syndrome was associated with a higher probability of sustained major molecular response (P=0.003) and showed a trend for a longer time to major molecular response loss (P=0.098). Positivity (defined as ≥ 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before imatinib discontinuation were associated with a higher probability of sustained major molecular response. Our data demonstrated that the occurrence of imatinib withdrawal syndrome after imatinib discontinuation and longer duration of imatinib were associated with a lower rate of molecular relapse. In addition, minimal residual leukemia measured by digital polymerase chain reaction had a trend for a higher molecular relapse. (Trial registered at ClinicalTrials.gov: NCT01564836).
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Song
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Choi
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Joon Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun, Hospital, Busan, Korea.
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Anyang, Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Zang
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Korea.
authors.forename: Sukjoong
authors.initials: S
authors.lastname: Oh
authors.affiliation: Division of Hematology and Cellular Therapy, Ulsan University Hospital, University of Ulsan College of Medicine, Daegu, Korea.
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, School of Medicine, Keimyung University, Daegu, Korea.
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Do
authors.affiliation: Division of Hematology-Oncology, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kwak
authors.affiliation: Department of Hematology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Hematology, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Yeung-Chul
authors.initials: YC
authors.lastname: Mun
authors.affiliation: Department of Internal Medicine, Inje University College of Medicine, Inje University Busan Paik Hospital, Ilsan, Korea.
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, National Health Insurance Service Ilsan Hospital, Ilsan, Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Chang
authors.affiliation: Department of Hematology, Gachon University Gil Hospital, Incheon, Korea.
authors.forename: Jinny
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Hematology-Oncology, Chungbuk National University Hospital, Cheongju, Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kwon
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea Catholic Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea dwkim@catholic.ac.kr.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D019233:Retreatment; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl