Therapy de-escalation before stopping in chronic myeloid leukaemia
Mené au Royaume-Uni sur 174 patients atteints d'une leucémie myéloïde chronique en phase de rémission stable, cet essai non randomisé de phase II (durée médiane de suivi : 6,9 ans) évalue l'intérêt et la faisabilité, du point de vue de la survie sans récidive, d'une désescalade de doses d'un traitement par inhibiteurs de tyrosine kinase (imatinib, nilotinib ou dasatinib) pendant 12 mois, avant l'arrêt complet du traitement pendant 2 ans
The treatment of chronic myeloid leukaemia has rapidly evolved since the invention of tyrosine kinase inhibitor (TKI) therapy. The efficacy of the first TKI, imatinib, was initially assessed in the IRIS trial (started in June, 2000) and was shown to be superior to previous treatments. To date, TKI therapy has been used for almost 20 years and the life expectancy of patients with chronic myeloid leukaemia treated with TKI therapy is equal to that of age-matched healthy controls. Initially, genetic and molecular responses and prevention of the accelerated phase of chronic myeloid leukaemia with TKI therapy were important treatment goals. These goals are still valid but, currently, when a patient is diagnosed with chronic phase chronic myeloid leukaemia, the treating physician will often discuss the possibility of treatment-free remission in the future. During the past 10 years, many treatment discontinuation trials have been done to assess the safety and efficacy of TKI discontinuation in patients with chronic myeloid leukaemia who have achieved deep molecular remission (at least MR4: BCR-ABL to ABL ratio <0·01% according to the international scale). The long-term follow-up of the STIM1 trial, one of the first discontinuation trials, showed that with a median follow-up of more than 6 years, 43% of patients were still in remission after TKI discontinuation. The EURO-SKI trial included over 700 patients and showed that at 24 months after TKI cessation the molecular relapse-free survival was 50%. Based on these positive results, some clinical guidelines state that TKI discontinuation can be considered in selected patients outside of the clinical trials. Prerequisites for safe TKI discontinuation have been suggested in guidelines by chronic myeloid leukaemia experts: chronic phase of the disease, at least 3–5 years of previous TKI therapy, quantifiable BCR-ABL1 transcript, access to high quality monitoring, and stable molecular response ( BCR-ABL1 ≤0·01% for >2 years).
The Lancet Haematology , commentaire, 2018