Towards chemotherapy-free treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia
Mené aux Etats-Unis sur 72 patients atteints d'une leucémie lymphoblastique aiguë Ph+, cet essai de phase II évalue l'efficacité, du point de vue de la réponse moléculaire complète et du taux de réponse globale, et la toxicité d'un traitement combinant ponatinib et blinatumomab
The addition of tyrosine kinase inhibitors (TKIs) to conventional chemotherapy backbones for adults with newly diagnosed Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia has substantially improved treatment outcomes. 1 , 2 However, the long-term outcomes are still unsatisfactory, with treatment-related resistance and toxicity. Over the past 10 years, several clinical trials have incrementally shown improved outcomes and reduced toxicity for these patients. These steps include the upfront use of the third-generation TKI ponatinib, which is active against the gatekeeper mutation, Thr315Ile, in the ABL1 tyrosine kinase domain. Circumventing this most frequent mechanism of resistance upon treatment with first and second-generation TKIs, such as imatinib and dasatinib, 2 led to improved outcome with a 3-year overall survival of 83% and higher rates of complete molecular response. 3 Reaching complete molecular response, defined as less than one leukemic blast in 10 000 mononuclear bone marrow cells, was shown to be strongly associated with improved overall survival in patients with Ph-positive acute lymphoblastic leukaemia who did not receive allogeneic haematopoietic stem-cell transplantation (HSCT) and is a useful primary endpoint for clinical trials. 4 To increase complete molecular response rates and overall survival, Foà and colleagues 5 used the bispecific anti-CD3–CD19 T-cell engager blinatumomab as a consolidation regimen after dasatinib plus glucocorticoid induction therapy in adults with newly diagnosed Ph-positive acute lymphoblastic leukaemia. Blinatumomab increased the percentage of patients who had a complete molecular response from 29% after induction to 60% after two blinatumomab cycles. 18-month overall survival was 95% (95% CI 90–100), and 38% of patients received HSCT
The Lancet Haematology , commentaire, 2021