Table 2 Summary of clinical trials examining treatment-free remission
From: A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase
Trial | Patient population | Key efficacy data | Key safety data |
|---|---|---|---|
Dasatinib DASFREE (NCT01850004) [66]: phase 2 trial of dasatinib therapy discontinuation in patients with CML-CP and stable MR4.5 | Aged ≥ 18 years Dasatinib treatment for ≥ 2 years as first-line or subsequent CML-CP therapy Dasatinib-induced DMR (MR4.5) for ≥ 1 year prior to enrollment ECOG PS 0–1 | TFR at 12 months (primary endpoint), overall: 48% Discontinuation after 1L dasatinib: 54% Discontinuation after 2L + dasatinib: 43% MMR at 24 months (secondary endpoint): 45% | 11% of patients (n = 9) experienced investigator-determined withdrawal events, including musculoskeletal pain and arterial hypertension |
Nilotinib ENESTop (NCT01698905) [69]: discontinuation of nilotinib in patients with BCR::ABL + CML-CP who have achieved sustained MR4.5 with nilotinib after imatinib | Aged ≥ 18 years 2L nilotinib for ≥ 2 years following imatinib BCR::ABL + CML-CP Lack of MR4.5 on imatinib Achieved MR4.5 on nilotinib ECOG PS 0–2 | TFR at 48 weeks (primary endpoint): 58% | Musculoskeletal pain within first 48 weeks of TFR reported in 42% of patients |
Nilotinib ENESTfreedom (NCT01784068) [70]: discontinuation of nilotinib in patients with b3a2/b2a2 CML-CP who have achieved sustained DMR with 1L nilotinib | Aged ≥ 18 years 1L nilotinib for ≥ 2 years CML-CP with b3a2 and/or b2a2 MR4.5 at screening ECOG PS 0–2 | TFR (MMR) at 48 weeks (primary endpoint): 52% | Musculoskeletal pain in first 48 weeks reported in 34% of patients |
Nilotinib ENESTgoal (NCT01744665) [105]: discontinuation of nilotinib in patients with CML-CP who have achieved sustained MR4.5 after switching to nilotinib | 1L imatinib for ≥ 1 year CML-CP with MMR but not MR4.5 Real-time qualitative polymerase chain reaction every 3 months | mRFS at 6 months: 7/17 patients sustained MR4.5 | 18% of patients experienced AEs during TFR |
Imatinib STIM (NCT00478987) [62]: observational study of CMR persistence after discontinuing imatinib therapy | Aged ≥ 18 years CML-CP CMR under treatment with imatinib for ≥ 2 years No prior treatments: immunomodulatory (except interferon α), autologous hematopoietic stem cell transplantation, or for other malignancies | TFR:  6 months: 43%  60 months: 38% | No musculoskeletal pain was reported 1 patient progressed to lymphoid blast crisis after relapsing and resuming TKI treatment |
Imatinib A-STIM (NCT02897245) [64]: observational study of MMR persistence after discontinuing imatinib therapy | CML-CP Treatment with imatinib CMR under treatment DMR (BCR::ABL1 International Scale ≤ 0.01%) | TFR without loss of major molecular response (primary outcome):  1 year: 57%  3 year: 53%  5 year: 51%  7 year: 46% | No safety outcomes reported |
1L TKI EURO-SKI (NCT01596114) [61]: phase 3, multicenter, open-label trial evaluating the persistence of MR in patients with CML after TKI discontinuation | Aged ≥ 18 years CML-CP with 1L TKI treatment or 2L if switched due to toxicity of 1L TKI  ≥ 3 years of prior TKI therapy  ≥ MR4 for ≥ 1 year | mRFS (primary endpoint):  6 months: 61%  24 months: 50%  49% patients lost MMR after TKI discontinuation | 4 deaths unrelated to CML:  1 of each: myocardial infarction, lung cancer, renal cancer, and heart failure 6 deaths unrelated to CML-CP after loss of MMR and treatment re-initiation |
1L TKI DESTINY (NCT01804985) [80]: UK, phase 2, open-label, multicenter trial of TKI de-escalation and stopping in patients with an excellent response to TKI treatment | Aged ≥ 18 years BCR::ABL1 + CML-CP  ≥ 3 years of prior TKI therapy  ≥ 3 qualitative polymerase chain reaction transcripts of < 0.1% BCR::ABL1 in the 12 months preceding enrollment | Relapse-free survival after 12 months de-escalation and 2 years of treatment discontinuation (primary endpoint):  Patients with MR4 at trial entry: 72%  Patients with MMR at trial entry: 36% | 2 deaths due to unrelated causes |