- permettre l’interruption du traitement chez un maximum de patients : déjà le nilotinib et le dasatinib en première ligne se sont révélés plus efficaces que l’imatinib avec des taux plus élevés de rémission cytogénétique complète et une rémission plus rapidement obtenue ainsi que des taux diminués de progression vers des phases accélérées ou acutisées. L’association de l’interféron pégylé à l’imatinib en première ligne entraîne une nette amélioration des résultats de l’imatinib. Les premiers essais d’association ITK2 + interféron pégylé débutent;
- réduire le risque de rechute après arrêt du traitement, ce qui nécessite le développement de nouvelles stratégies ciblant la cellule souche leucémique.
Chronic myeloid leukaemia is a model of how the molecular understanding of a disease can transform the therapy and the monitoring. imatinib which targets the oncogene product BCR ABL has transformed the natural history of this disease during the last decade. The recognition that some patients develop mutations within BCR-ABL induced the development of the second generation tyrosine kinase inhibitors (TKI), nilotinib and dasatinib. Both compounds are more potent than imatinib and have prooved effective in patients with CML in failure with imatinib. T315I mutation on BCR-ABL confers resistance to all three drugs. Third generation of TKI is now appearing, targeting this highly resistant mutation. Imatinib can be safely discontinued in patients with complete molecular remission of at least two years duration; a longer follow up is needed but the 40 % of patients who had not relapsed are highly promising. Within the next years a cure of patients may been considered if two conditions are fullfilled:
- make the treatment discontinuation available for all patients: nilotinib and dasatinib for newly diagnosed chronic myeloid leukemia are superior to imatinib with higher rates of complete cytogenetic remission, faster time to remission, and reduced rates of progression to accelerated phase or blast crisis. The addition of Peg Interferon α2A to imatinib therapy in first line, results in significantly higher rates of molecular response;
- decrease the probability of relapse after treatment discontinuation with strategies targeting the leukemic stem cell.