Evidence of several studies suggest that patients who have achieved a sustained stable deep molecular response (DMR) as MR4 and MR4.5 can be safely discontinued with close monitoring without relapse, despite BCR/ABL1 DNA remaining detectable. In Brazil, CML patients have received almost exclusively Imatinib as first-line treatment. However, in both scenarios there is a limit coverage of PCR exams/ year which allows for adequate monitoring but it is not sufficient for the implementation of TFR safely in eligible patients.

To report a Brazilian single institution Imatinib discontinuation trial and to evaluate factors impacting treatment -free response (TFR) and treatment free survival (TFS) provided by own founds.

From 2020 -2021, 26 eligible patients were invited to participate in a single arm trial of Imatinib discontinuation (DIP). Inclusion criteria: age > 18 years, chronic phase, minimum of 04 years of Imatinib therapy, deep molecular response sustained > or = 02 years (confirmed by 04 tests in the last two years, defined MR4.0 or MR 4.5 and a confirmatory exam at the moment of the screening). Atypical transcripts were excluded. After discontinuation, patients were monitored by RT- PCR monthly in the first year, every two months in the second year and every three months since the third year. Criteria for Imatinib re-initiation: loss of MMR confirmed by two exams, loss of cytogenetic response, loss of hematologic response, disease progression. TFR was calculated from the date of discontinuation until first event: loss of MMR, Imatinib reintroduction, death any cause or last follow up. TFS was calculated from the date of imatinib discontinuation until reintroduction or last follow- up (censoring deaths not related to CML). The costs of exams were provided by own founds of our institution.

From 26 patients, 20 patients agreed to consent inform to discontinuation of imatinib. 06 patients declined despite information because their insecurity about TFR. Twelve patients (60%) presented MR4. Median age was 52.3 years old and 13 (65%) were female. Median time diagnosis to discontinuation of imatinib 8.04(4.6-15.5) years. Twelve (60%) patients sustained TFR. Seven patients of twelve had presented MR 4 and five had MR 4.5 in the screening, respectively. (p = 0,85). It means 58,3% of the total of patients with MR 4 and 62,5% with MR 4.5. In this interim analysis the median time of follow up was 14.5 (2.7-18.8) months. One patient died due to COVID19 with major molecular response (MMR). Eight (40%) lost MMR and imatinib was restarted. In this group the median time until MMR loss was 7.24 (2.1-13.8) months. At this moment, 07 patients (87,5 %) recovered MMR. In addition, in this group 06 patients (75%) achieved the same level of MR with reintroduction of imatinib with median 5.2 (3.7-6.3) months. Regarding adherence, 4 (20%) had some absences in monthly medical consultations and 1(5%) missed follow-up. Fifteen tests (6.14%) were performed to confirm MR loss, however only in 8 tests (53.3%) were confirmed. In fact, 04 patients (33,33%) still in TFR because of the double confirmatory test. There was no transformation to advanced phases. Gender, age at de diagnosis, age at discontinuation, Sokal, BCR-ABL trasncripts type, duration of Imatinib therapy, duration of MR 4.0 or MR4.5 did not affect TFR. Withdrawal syndrome occurred in 05 patients (25%); 04 patients with grade 1 and 01 patient with grade 2, had been used corticosteroid for few days.

The preliminary results of this trial demonstrated the feasibility and safety of Imatinib discontinuation, even using Brazilian copies, and the results were similar of that presented in another trials.