Table 3.

Clinical trials of TKI discontinuation in patients with CML-CP and deep molecular response

TrialTreatment before d/c (response required for d/c)Definition of relapseRelapse-free pts, % (median f/u, mo)Patients responding to TKI after relapse
Trials of IM d/c
STIM (ref. 40; N = 100)IM for ≥36 mo (MR5 for ≥24 mo)Confirmed loss of MR539% (30)56/61 regained MR5
ALLG CML8/TWISTER (ref. 55; N = 40)IM for ≥36 mo (MR4.5 for ≥24 mo)Confirmed loss of MR4.545% (42)22/22 regained MMRa
According to STIM (ref. 41; N = 66)IM for ≥36 mo (MR4.5 for ≥24 mo)Loss of MMR64% (23)24/24 regained MMRa
Korean study (ref. 78; N = 48)IM for ≥36 mo (CMR for ≥24 mo)Confirmed loss of MMR81% (15.8)8/9 regained MMRa
Yhim et al. (ref. 54; N = 14)IM for median 56.4 mo; range, 26.2–82.0 (CMR for ≥12 mo)Confirmed loss of CMR28.6% at 12 mo (23)7/10 regained CMR
Keio STIM (ref. 79; N = 40)IM for median 98 mo; range, 24–126 (UMRDb for ≥24 mo)Loss of UMRDb55.4% at 12 mo (15.5)17/18 regained CMR
Takahashi et al. retrospective analysis (ref. 80; N = 43)IM for median 45.2 mo; range, 4.5–92.7 [UMRD (≥4-log sensitivity) by RQ-PCR, RT-PCR, or TMA]Molecular recurrence after d/c of IM for ≥6 mo56% (22.4)17/17 regained MMRa
STIM 2c (ref. 57; N = 200)IM (MR5 for ≥2 y)Loss of MMR and/or >1-log increase in BCR–ABL1Study ongoingStudy ongoing
Trials of NIL d/c
Nilo post-STIMc (ref. 57; N = 70)NIL for ≥2 y in patients who failed TFR in STIM or STIM 2 (confirmed CMR after 2 y of NIL)Loss of MR5 on 2 consecutive assessmentsStudy ongoingStudy ongoing
ENESTFreedomc (ref. 57; N = 175)First-line NIL for ≥2 y and 1 y NIL on study (MR4.5 for ≥1 y)Loss of MMRStudy ongoingStudy ongoing
ENESTopc (ref. 57; N = 117)TKI therapy for ≥3 y, including ≥2 y of second-line NIL and 1 y NIL on study (MR4.5 for ≥1 y)Confirmed loss of MR4 or any loss of MMRStudy ongoingStudy ongoing
ENESTgoalc (ref. 57; N = 300)IM for ≥1 y and NIL on study (MR4.5 for 1 or 2 y)Confirmed loss of MR4Study ongoingStudy ongoing
ENESTPathc (ref. 57; N = 1,058)IM for ≥2 y and NIL on study (MR4 for 1 or 2 y)Loss of MR4Study ongoingStudy ongoing
TIGERc (ref. 57; N = 652)First-line NIL + PEG-IFN-α vs. NIL for ≥2 y on study, then PEG-IFN-α vs. NIL maintenance therapy (stable MR4)Loss of MMRStudy ongoingStudy ongoing
Trials of DAS d/c
DASFREEd (57) (N = 75)DAS for ≥2 y (MR4.5 for ≥1 y)Loss of MMRStudy ongoingStudy ongoing
Trials of TKI d/c
STOP 2G-TKI (ref. 42; N = 34)NIL or DAS for ≥36 mo (UMRD for ≥24 mo, with ≥20,000 ABL1 copies)Loss of MMR58.3% at 12 mo (14)13/15 regained MMR
10/13 regained CMR
EURO-SKId (ref. 57; N = 500)TKI therapy (first-line or second-line) for ≥3 y (MR4 for ≥1 y)Loss of MMRStudy ongoingStudy ongoing
DESTINYd (ref. 57; N = 168)IM, NIL, or DAS for ≥3 y and half-standard dose of TKI for 1 y on study (MMR or MR4 for ≥1 y at therapeutic dose and 1 y at half-standard dose)Loss of MMRStudy ongoingStudy ongoing
NCT00573378c (ref. 57; N = 40)NIL or IM for ≥3 y, with stable dose for ≥1 y and same TKI + PEG-IFN-α for 2 y on study (NR)NRStudy ongoingStudy ongoing

Abbreviations: ALLG, Australasian Leukaemia and Lymphoma Group; DAS, dasatinib; d/c, discontinuation; f/u, follow-up; IM, imatinib; MR, molecular response; NIL, nilotinib; NR, not reported; PEG-IFN-α, pegylated interferon-α; RT-PCR, nested reverse transcriptase PCR; TMA, transcription-mediated amplification; UMRD, undetectable minimal residual disease.

  • aPatients achieved this level of response or better.

  • bUMRD defined as <100 copies by TMA; thus, loss of UMRD was >100 copies by TMA.

  • cCurrently recruiting participants.

  • dNot yet recruiting participants.