Predictive indicators of successful tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia

Table 1 Summary of level (depth) of molecular response required prior to discontinuation attempt in discontinuation clinical trials, for all of these studies, molecular relapse was considered to be loss of major molecular response

Molecular response	Trial	TKI	TFR, %	TFR at month
MMR	Destiny	Dasatinib	39	24
DMR	JALSG-STIM213	Imatinib	68	12
DMR	DASFREE	Dasatinib	63	12
DMR	ENESTFreedom	Nilotinib	52	12
DMR	ENESTop	Nilotinib	58	12
DMR	EURO-SKI	Mixed	61	6
CMR1	STIM12	Imatinib	43	6
UMRD	ISAV3	Imatinib	48	36
UMRD	STOP 2G-TKI4	Mixed	61	12
UMRD	STIM25	Imatinib	64	6
UMRD	KIDS6	Imatinib	62	12
UMRD	TWISTER6	Imatinib	47	24

¹Complete molecular response should not be detectable but could be MR⁴ or MR^4.5 depending on the sensitivity of the BCR-ABL1 transcript quantification technique used[63].

²> 5-log reduction.

³Limit of detection log4-4.5.

⁴Undetectable BCR-ABL1 by real-time quantitative polymerase chain reaction, with at least 20,000 copies of the control gene.

⁵Undetectable BCR-ABL1 with sensitivity ≥ 50000 amplified copies of ABL1 control gene.

⁶Limit of detection log4.5. CMR: Complete molecular response; DMR: Deep molecular response MR⁴ or better (< 0.01%); MMR: Major molecular response, MR³ (0.1%); TFR: Treatment free remission; TKI: Tyrosine kinase inhibitor; UMRD: Undetectable molecular residual disease.

Table 2 Inclusion and exclusion criteria for patient selection from the Canarian-chronic myeloid leukemia “Tyrosine kinase inhibitor treatment discontinuation in patients with chronic-phase chronic myeloid leukemia” protocol

Inclusion criteria, all should be met	Exclusion criteria
Aged 18 yr or over, with diagnosis of CML in chronic phase	Resistance to any TKI or insufficient response to imatinib
Received 5 yr or more of TKI treatment (imatinib, bosutinib, nilotinib or dasatinib)	Accelerated phase or blastic crisis in any moment
Maintained a MR4.5 (BCR-ABL1/ABL1 < 0.0032%) or better in all samples taken during the last 3 yr (with at least one recent sample certified in a centralized laboratory)	Detection of BCR-ABL1 kinase domain mutations in any moment
Present a typical BCR-ABL1 transcript at diagnosis that permits quantifiable molecular monitoring
A low or intermediate Sokal index at diagnosis
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CML: Chronic myeloid leukemia; MR: Molecular response; TKI: Tyrosine kinase inhibitor.