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TKI discontinuation in CML clinical practice
Results
Patients
We collected data on 293 patients who discontinued TKI between June 2003 and February 2016. Overall, 34 of 293 patients (11.5%) suspended treatment because they were enrolled in the prospective interventional Imatinib Suspension and Validation (ISAV) study.13 All the other patients discontinued as per clinical practice, and the rea-
sons were: toxicity (20%, 58 of 293), pregnancy (6%, 17 of 293), and a shared decision between the treating physi- cian and the patient (62%, 182 of 293). Finally, one patient discontinued the TKI because of chemotherapy for anoth- er neoplasia. Reason of discontinuation was not known for one patient.
Patients’ characteristics are reported in Table 1. Median age was 49 years (IQR 38-60) at diagnosis and 59 years (IQR 48-70) at discontinuation. At the time of discontinu-
Table 1. Patients’ baseline characteristics. N
Age at diagnosis (median [IQR])
Age at discontinuation (median [IQR]) Sex
Males (%)
Sokal Score n=263 (%)
Low Intermediate High
Type of transcript n=252 (%)
b2a2 b2a3 b3a2 b3a3 e1a2
Last TKI (%) n=293 Imatinib
Nilotinib Dasatinib Bosutinib
Line of treatment at discontinuation (%) n=293
1st line 2nd line 3rd line 4th line
Reasons for discontinuation (%) n=292 Shared decision
Toxicity
ISAV13
Pregnancy
Chemotherapy for 2nd tumor
MR at discontinuation (%) n=290
MR4 MR4.5 MR5
Transcript undetectable
Duration of last TKI (median [IQR])
Duration of treatment with any TKI (median [IQR]) Duration of total treatment (median [IQR])
Time to DMR (median [IQR])
Duration of DMR (median [IQR])
Imatinib
211
47 [36, 58] 58 [46,67]
117 (56)
114 (61) 52 (28) 20 (11)
42 (23) 0 (0) 141 (76.5) 1 (0.5) 0 (0)
211 (100) 0 (0)
0 (0)
0 (0)
129 (61) 81 (38.5) 1 (0.5) 0 (0)
135 (64) 28 (13.5) 34 (16) 12 (6) 1 (0.5)
70 (33) 61 (29) 41 (20) 37 (18) 96 [62, 120] 96 [62, 120] 104 [73, 142] 24 [12, 52] 53 [33, 82]
2nd generationTKI
82
55 [45, 67] 63 [51, 74]
44 (54)
40 (52) 28 (36) 9 (12)
20 (29) 1 (1.5) 46 (68) 0 (0) 1 (1.5)
0 (0) 58 (71) 23 (28) 1 (1)
33 (40) 36 (44) 12 (15) 1 (1)
47 (57) 30 (37) 0 (0) 5 (6) 0 (0)
31 (38) 29 (36) 12 (15)
9 (11) 50 [32, 66] 73 [51, 98] 76 [52, 109] 13 [6, 26] 36 [25, 46]
Overall
293
49 [38, 60] 59 [48, 70]
161 (55)
154 (59) 80 (30) 29 (11)
62 (24.5) 1 (0.5) 187 (74) 1 (0.5) 1 (0.5)
211 (72) 58 (19.5) 23 (8) 1 (0.5)
162 (55) 117 (40) 13 (4.5) 1 (0.5)
182 (62) 58 (20) 34 (11.5) 17 (6) 1 (0.5)
101 (35) 90 (31) 53 (18) 46 (16) 77 [54, 111] 87 [59, 117] 98 [65, 133] 21 [10, 42] 46 [30, 73]
P
0.001 0.023 0.884
0.346
0.126
<0.001
<0.001
<0.001
0.315
<0.001 0.002 <0.001 <0.001 <0.001
IQR: interquartile ranges; TKI: tyrosine kinase inhibitor; MR: molecular response; DMR: deep molecular response.
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