PB1905: FEASIBILITY OF TREATMENT DISCONTINUATION IN CHRONIC MYELOID LEUKEMIA IN CLINICAL PRACTICE: RESULTS FROM A SERIES OF 19 PATIENTS

Abstract

Background: The therapeutic of chronic myeloid leukemia (CML) has profoundly changed over the past years. Patients have now almost normal life expectancy with an excellent quality of life The main goal is to achieve a stable deep molecular response (DMR) and to discontinue medication for treatment-free remission (TFR) for patients with chronic phase CML (CP-CML). The data from the published literature demonstrate that 40–60% of patients achieve TFR, with relapses risk occurring within the first six months, almost all patients who relapsed regained a molecular response upon retreatment, indicating TKI discontinuation is safe. The ELN defines DMR as undetectable BCR–ABL1 mRNA transcripts in the blood using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and/or two consecutive high-quality PCR samples with >104 sensitivity. For patients aiming at TFR, the optimal response (at any time) is BCR-ABL1 ≤ 0.01% (MR4) for at least two years. The loss of MMR (BCR-ABL1 > 0.1%) indicates failure after TFR Aims: to follow patients having CML-CP who have achieve DMR 4.0 or more for at least two years, to allow TKl discontinuation with TFR as an aim. Methods: This is a retrospective cohort study of patients diagnosed with CML-CP in Hematology department The study was approved by an ethical review authority of the medical department. All consenting patients with a reported diagnosis of CML-CP between 1 January 2009 and 31 December 2016 and whiling an TKI discontinuation were identified. Data regarding patients with TKI treatment interruption were gathered as follows: last TKI prior to discontinuation, date of discontinuation, time to DMR and duration of treatment by lmatib before discontinuation, BCR-ABL1 IS (International Scale) percentage prior to at least 2 years beforeTKI discontinuation, if patient had re-initiated TKI treatment, date and reason of re-initiation and if the patient had progress to AP or BP An intensive monitoring is recommended earlier in the first six months after stopping TKI discontinuation. A peripheral blood monitoring with PCR analysis every 4 weeks for 6 months, then every 8 weeks for 12 months, then every 3 months thereafter. TKI was re-initiated at any time if loss of MMR First-line therapy is based on a TKI; imatinib brand is not available in Algeria so we use generics, dasatinib and nilotinib are the only other ITKs but not approved as first line therapy. Statistical methods were treated by IBM SPSS statistics 26 Results: were included for analysis 19 patients. Date of treatment discontinuation was between January and December 2019, last follow-up was 1st January 2022 and median follow-up time was 15 months from discontinuation (range 4–34 months). All patients received lmatib as first line therapy at a dose of 400 MG/day and they have all achieved a stable DMR for two (or more) years. All patients who relapsed regained a molecular response upon retreatment, despite one who progressed to AP. 35,8% have maintained a molecular remission after discontinuation. Summary/Conclusion: Compared to the first prospective proof of concept for stopping TKI treatment, the Stop Imatinib 1 (STIM1) trial which showed that 38% of the patients maintained a molecular remission after a median follow-up of 77 months, we notice in this small cohort that although we did not reach the median of fallow up that our results are quiet similar. In our country generic imatinib(Imatib) is the cost-effective initial treatment in CML-CP.