Table 2. Summary of TKI discontinuation studies.
Adapted from Saußele S, Richter J, Hochhaus A, et al. The concept of treatment-free remission in chronic myeloid leukemia. Leukemia 2016; 30(8):1641; with permission.
| Trial | Patients reported | Treatment prior to discontinuation | Eligibility for TKI discontinuation by MR | Threshold for restarting TKI | TFR% (median follow-up time) | |
|---|---|---|---|---|---|---|
| Imatinib discontinuation trials | ||||||
| STIM1 | 100 | Imatinib +/− prior IFN | MR5(≥2y) | ≥2 consecutive samples with detectable PCR and a 1-log increase | 39% (55m) | |
| STIM2 | 124 | Imatinib | MR4.5(≥2y) | ≥2 consecutive samples with detectable PCR and a 1-log increase | 46% (2y) | |
| TWISTER | 40 | Imatinib +/− prior IFN | MR4.5(≥2y) | Detectable PCR | 45% (42m) | |
| A-STIM | 80 | Imatinib +/− prior IFN | Undetectable PCR (≥2y) with low level positives occasionally allowed | Loss of MMR | 64% (23m) | |
| ISAV | 112 | Imatinib | Undetectable PCR (18 months) | Loss of MMR | 51.9% at 36 months (21m) | |
| KID | 90 | Imatinib +/− prior IFN | MR4.5(≥2y) | Loss of MMR | 50% (26.6m) | |
| HOVON | 18 | Imatinib | MR4.5(≥2y) | Detectable PCR | 33% (36m) | |
| Imatinib and/or 2G-TKI discontinuation trials | ||||||
| STOP-2G TKI | 52 | Nilotinib or dasatinib | MR4.5(≥2y) | Loss of MMR | 61% (6m); ongoing | |
| ENEST Freedom | 190 | Nilotinib | MR4.5(≥1y) | Loss of MMR | 51.6% (week 48);ongoing | |
| ENESTop | 126 | 2nd-line Nilotinib | MR4.5(≥1y) | Loss of MMR or confirmed loss of MR4 | 57.9% (week 48);ongoing | |
| ENEST Path | 1058 (estimated) | Imatinib followed by Nilotinib | MR4 (≥1–2y) | Loss of MMR or confirmed loss of MR4 | Ongoing | |
| ENEST Goal | 300 (estimated) | Imatinib without MMR followed by Nilotinib | MR4.5(≥1–2y) | Confirmed loss of MR4 | Ongoing | |
| DADI | 63 | Second-line dasatinib | MR4(≥1y) | Loss of MR4 | 49% (6m) | |
| DASFREE | 79(estimated) | Dasatinib | MR4.5(≥1y) | Loss of MMR | Ongoing | |
| CML V (TIGER) | 652(estimated) | Nilotinib vs. Nilotinib + IFN | MR4((≥1y) | Loss of MMK | Ongoing | |
| LAST | 173(estimated) | Imatinib, nilotinib, dasatinib or bosutinib | MR4(≥2y) | Detectable PCR | Ongoing | |
| DESTINY | 168 (estimated) | Imatinib, nilotinib or dasatinib | Patients in MMR or MR4 (≥ly) who can maintain MMR response on half-dose TKI for 12 months | Loss of MMR | Ongoing | |
| EURO-SKI | 200 | Imatinib, nilotinib or dasatinib | MR4((≥1y) | Loss of MMR | 61% (6m); ongoing | |