Dasatinib plus sequential CD19/CD22 CAR T-cell therapy in adult patients with newly diagnosed Ph+ ALL

Combined TKI and CAR T-cell therapy has markedly improved outcomes in RR Ph+ ALL. However, it remains to be determined whether this combination can produce high rates of complete molecular remission (CMR) and leukemia-free survival (LFS) in newly diagnosed Ph+ ALL.¹

A recent phase II trial assessed the efficacy and safety of the TKI dasatinib in combination with CAR T-cell therapy in adult patients with newly diagnosed Ph+ ALL (N = 28). Patients were assigned to receive induction with dasatinib, vindesine, and dexamethasone, followed by sequential CD19 and CD22 CAR T-cell therapies and dasatinib maintenance. The primary endpoint was CMR after CD19 CAR T-cell therapy. Secondary endpoints included CMR after CD22 CAR T-cell therapy, LFS, OS, and safety. Results were published by Zhang et al. in JAMA Oncology.¹

Key learnings 

The CMR rate was 25% after induction and increased to 85% (p < 0.001) after CD19 CAR T-cell therapy. Sequential CD22 CAR T-cell therapy in 25 patients resulted in a CMR rate of 76%. 

At a median follow-up of 23.9 months, 2-year OS and LFS were both 92%. Hematological relapses occurred in two patients, both of whom had IKZF1 deletions at baseline.

The safety profile was favorable, with only Grade 1 CRS events (in 21/52 patients who received CAR T-cell therapy). No ICANS events reported, and notably, no CNS relapses occurred despite limited intrathecal chemotherapy.

Overall, encouraging efficacy and safety data from the phase II study suggest that the combination of dasatinib and CAR T-cell therapy could be a viable chemotherapy-free treatment option for newly diagnosed adult patients with Ph+ ALL.