Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia
Mené sur 268 patients adultes atteints d'une leucémie lymphoblastique aiguë Ph+, cet essai randomisé franco-suisse évalue l'efficacité, du point de vue du taux de réponse moléculaire majeure, d'un traitement d'induction combinant une chimiothérapie d'intensité réduite et l'imatinib
Initial imatinib-based therapy of Ph-positive adult ALL is associated with lower early mortality and higher CR rate.In adults with Ph+ ALL, allo-SCT in CR1 prolongs RFS and OS, even if some favorable patients may have a similar outcome after auto-SCT. In this study, we randomly compared high doses of the tyrosine kinase inhibitor (TKI) imatinib combined with reduced-intensity chemotherapy (arm A) to standard imatinib/HyperCVAD treatment (arm B) in 268 adults (median age, 47 years) with Ph-positive acute lymphoblastic leukemia (ALL). The primary objective was the major molecular response (MMolR) rate after cycle 2, patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor or autologous SCT if in MMolR and no donor. With less induction deaths, the CR rate was higher in arm A (98% versus 91%, P= 0.006), while MMolR rate was similar in both arms (66% versus 64%). With a median follow-up of 4.8 years, 5-year EFS and OS were estimated at 37.1% and 45.6% respectively, without difference between both arms. Allogeneic transplantation was associated with a significant benefit in RFS (HR, 0.69; P= 0.036) and OS (HR, 0.64; P= 0.02), initial WBC being the only factor significantly interacting with this SCT effect. In patients achieving MMolR, outcome was similar after autologous and allogeneic transplantation. This study validates an induction regimen combining reduced-intensity chemotherapy and imatinib in Ph-positive ALL adult patients and suggests that SCT in first CR is still a good option in Ph-positive ALL adult patients. The study is registered to www.ClinicalTrials.gov as NCT00327678.
Blood 2015