Objectives: To assess interruptions/discontinuations of tyrosine kinase inhibitor (TKI) treatment in Belgian patients with chronic myeloid leukaemia (CML). Methods: This retrospective study included patients with TKI interruptions/discontinuations of ≥4 continuous weeks (no clinical trial context) between May 2013 and May 2016. Data collection took place between October 2016 and February 2017. Results: All 60 participants (69 interruptions/discontinuations) had chronic-phase CML and 75% had at least a major molecular response (≥MMR) at interruption/discontinuation. Most interruptions/discontinuations occurred while on imatinib (36/69; 49%) and dasatinib (20/69; 29%). Most interruptions/discontinuations occurred due to side effects/intolerance (46/69; 67%); other reasons included a wish to conceive (6/69; 9%) and attempts to achieve treatment-free remission (TFR) (6/69; 9%). Interruptions due to side effects occurred later for imatinib- or dasatinib-treated patients than for those on nilotinib or ponatinib. Treatment was re-initiated in 62% (43/69) of cases. Most interruptions caused by side effects/intolerance were followed by treatment changes. All 4 patients with ≥MR 4.5 at interruption/discontinuation and ≥11-month follow-up who had not restarted treatment maintained the response. Conclusion: Although TKIs are used for long-term CML treatment, physicians sometimes recommend interruptions/discontinuations. In this study, interruptions/discontinuations were mainly caused by side effects or intolerance, rather than TFR attempts.

1.
Chopade
P
,
Akard
LP
.
Improving Outcomes in Chronic Myeloid Leukemia Over Time in the Era of Tyrosine Kinase Inhibitors
.
Clin Lymphoma Myeloma Leuk
.
2018
Nov
;
18
(
11
):
710
23
.
[PubMed]
2152-2650
2.
Steegmann
JL
,
Baccarani
M
,
Breccia
M
,
Casado
LF
,
García-Gutiérrez
V
,
Hochhaus
A
, et al
European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia
.
Leukemia
.
2016
Aug
;
30
(
8
):
1648
71
.
[PubMed]
0887-6924
3.
Rea
D
.
Management of adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukemia
.
Ann Hematol
.
2015
Apr
;
94
(
S2
Suppl 2
):
S149
58
.
[PubMed]
0939-5555
4.
Palani
R
,
Milojkovic
D
,
Apperley
JF
.
Managing pregnancy in chronic myeloid leukaemia
.
Ann Hematol
.
2015
Apr
;
94
(
S2
Suppl 2
):
S167
76
.
[PubMed]
0939-5555
5.
Jiang
Q
,
Liu
ZC
,
Zhang
SX
,
Gale
RP
.
Young age and high cost are associated with future preference for stopping tyrosine kinase inhibitor therapy in Chinese with chronic myeloid leukemia
.
J Cancer Res Clin Oncol
.
2016
Jul
;
142
(
7
):
1539
47
.
[PubMed]
0171-5216
6.
Marin
D
,
Bazeos
A
,
Mahon
FX
,
Eliasson
L
,
Milojkovic
D
,
Bua
M
, et al
Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib
.
J Clin Oncol
.
2010
May
;
28
(
14
):
2381
8
.
[PubMed]
0732-183X
7.
Noens
L
,
van Lierde
MA
,
De Bock
R
,
Verhoef
G
,
Zachée
P
,
Berneman
Z
, et al
Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study
.
Blood
.
2009
May
;
113
(
22
):
5401
11
.
[PubMed]
0006-4971
8.
Cortes
J
,
O’Brien
S
,
Kantarjian
H
.
Discontinuation of imatinib therapy after achieving a molecular response
.
Blood
.
2004
Oct
;
104
(
7
):
2204
5
.
[PubMed]
0006-4971
9.
Mauro
MJ
,
Druker
BJ
,
Maziarz
RT
.
Divergent clinical outcome in two CML patients who discontinued imatinib therapy after achieving a molecular remission
.
Leuk Res
.
2004
May
;
28
Suppl 1
:
S71
3
.
[PubMed]
0145-2126
10.
Merante
S
,
Orlandi
E
,
Bernasconi
P
,
Calatroni
S
,
Boni
M
,
Lazzarino
M
.
Outcome of four patients with chronic myeloid leukemia after imatinib mesylate discontinuation
.
Haematologica
.
2005
Jul
;
90
(
7
):
979
81
.
[PubMed]
1592-8721
11.
Mahon
FX
,
Réa
D
,
Guilhot
J
,
Guilhot
F
,
Huguet
F
,
Nicolini
F
, et al;
Intergroupe Français des Leucémies Myéloïdes Chroniques
.
Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial
.
Lancet Oncol
.
2010
Nov
;
11
(
11
):
1029
35
.
[PubMed]
1470-2045
12.
Mahon
FX
,
Réa
D
,
Guilhot
J
,
Guilhot
F
,
Huguet
F
,
Nicolini
FE
, et al
Discontinuation of Imatinib in Patients with Chronic Myeloid Leukemia Who Have Maintained Complete Molecular Response: Update Results of the STIM Study. American Society of Hematology 53rd Annual Meeting; 2011 Dec 10–13; San Diego, CA, USA
.
Blood
.
2011
;
118
(
21
):
603
.0006-4971
13.
Mahon
FX
,
Réa
D
,
Guilhot
J
,
Guilhot
F
,
Huguet
F
,
Nicolini
FE
, et al
Long Term Follow-Up After Imatinib Cessation For Patients Indeep Molecular Response: The Update Results Of The STIM1 Study. American Society of Hematology 55th Annual Meeting; 2013 Dec 7–13; New Orleans, LA, USA
.
Blood
.
2013
;
122
(
21
):
255
.0006-4971
14.
Ross
M
,
Branford
S
,
Seymour
J
,
Arthur
C
,
Schwarer
A
,
Dang
P
, et al
Frequent and sustained drug-free remission in the Australian CML8 trial of imatinib withdrawal. 17th Congress of the European Hematology Association; 2012 Jun 14–17; Amsterdam, The Netherlands
.
[abstract 0189]
.
Haematologica
.
2012
;
97
Suppl 1
:
74
.0390-6078
15.
Ross
DM
,
Branford
S
,
Seymour
JF
,
Schwarer
AP
,
Arthur
C
,
Yeung
DT
, et al
Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study
.
Blood
.
2013
Jul
;
122
(
4
):
515
22
.
[PubMed]
0006-4971
16.
Rousselot
P
,
Charbonnier
A
,
Cony-Makhoul
P
,
Agape
P
,
Nicolini
FE
,
Varet
B
, et al
Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease
.
J Clin Oncol
.
2014
Feb
;
32
(
5
):
424
30
.
[PubMed]
0732-183X
17.
Hochhaus
A
,
Masszi
T
,
Giles
FJ
,
Radich
JP
,
Ross
DM
,
Gómez Casares
MT
, et al
Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study
.
Leukemia
.
2017
Jul
;
31
(
7
):
1525
31
.
[PubMed]
0887-6924
18.
Mahon
FX
,
Boquimpani
C
,
Kim
DW
,
Benyamini
N
,
Clementino
NC
,
Shuvaev
V
, et al;
Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase Results From a Single-Group
.
Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2, Open-Label Study
.
Ann Intern Med
.
2018
Apr
;
168
(
7
):
461
70
.
[PubMed]
0003-4819
19.
Rea
D
,
Nicolini
FE
,
Tulliez
M
,
Rousselot
P
,
Guilhot
F
,
Gardembas
M
, et al
Dasatinib or nilotinib discontinuation in chronic phase (CP)- chronic myeloid leukemia (CML) patients (pts) with durably undetectable BCR-ABL transcripts: interim analysis of the STOP 2G-TKI study with a minimum follow-up of 12 months—on behalf of the French CML Group Filmc. Blood.
2014
;124(21). Abstract no. 811.
20.
Imagawa
J
,
Tanaka
H
,
Okada
M
,
Nakamae
H
,
Hino
M
,
Murai
K
, et al;
DADI Trial Group
.
Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained deep molecular response for longer than 1 year (DADI trial): a multicentre phase 2 trial
.
Lancet Haematol
.
2015
Dec
;
2
(
12
):
e528
35
.
[PubMed]
2352-3026
21.
Shah
NP
,
García-Gutiérrez
JV
,
Jiménez-Velasco
A
,
Larson
S
,
Saussele
S
,
Rea
D
, et al
Updated 18-Month Results from Dasfree: A Study Evaluating Dasatinib Discontinuation in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) and Deep Molecular Response (DMR)
.
Blood
.
2018
;
132
:
4253
.0006-4971
22.
Breccia
M
,
Foà
R
.
Current Information and Recommendations on the Discontinuation of TKI Inhibitors in Chronic Myeloid Leukemia
.
Curr Oncol Rep
.
2018
Mar
;
20
(
3
):
23
.
[PubMed]
1523-3790
23.
Baccarani
M
,
Deininger
MW
,
Rosti
G
,
Hochhaus
A
,
Soverini
S
,
Apperley
JF
, et al
European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013
.
Blood
.
2013
Aug
;
122
(
6
):
872
84
.
[PubMed]
0006-4971
24.
Hughes
TP
,
Ross
DM
.
Moving treatment-free remission into mainstream clinical practice in CML
.
Blood
.
2016
Jul
;
128
(
1
):
17
23
.
[PubMed]
0006-4971
25.
Pallera
A
,
Altman
JK
,
Berman
E
,
Abboud
CN
,
Bhatnagar
B
,
Curtin
P
, et al
NCCN Guidelines Insights: Chronic Myeloid Leukemia, Version 1.2017
.
J Natl Compr Canc Netw
.
2016
Dec
;
14
(
12
):
1505
12
.
[PubMed]
1540-1405
26.
Vardiman
JW
,
Thiele
J
,
Arber
DA
,
Brunning
RD
,
Borowitz
MJ
,
Porwit
A
, et al
The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes
.
Blood
.
2009
Jul
;
114
(
5
):
937
51
.
[PubMed]
0006-4971
27.
Benghiat
F
,
Beguin
Y
,
Dessars
B
,
Devos
T
,
Lewalle
P
,
Mineur
P
, et al
Practical management of chronic myeloid leukaemia in Belgium
.
Belgian Journal of Hematology.
2015
;
6
(
1
):
16
32
.
28.
Vrijens
B
,
De Geest
S
,
Hughes
DA
,
Przemyslaw
K
,
Demonceau
J
,
Ruppar
T
, et al;
ABC Project Team
.
A new taxonomy for describing and defining adherence to medications
.
Br J Clin Pharmacol
.
2012
May
;
73
(
5
):
691
705
.
[PubMed]
0306-5251
29.
Shash
E
,
Bassi
S
,
Cocorocchio
E
,
Colpi
GM
,
Cinieri
S
,
Peccatori
FA
.
Fatherhood during imatinib
.
Acta Oncol
.
2011
Jun
;
50
(
5
):
734
5
.
[PubMed]
0284-186X
30.
Oweini
H
,
Otrock
ZK
,
Mahfouz
RA
,
Bazarbachi
A
.
Successful pregnancy involving a man with chronic myeloid leukemia on dasatinib
.
Arch Gynecol Obstet
.
2011
Jan
;
283
(
1
):
133
4
.
[PubMed]
0932-0067
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.