Relapsed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia responds well to a combination of modified hyper‐CVAD, blinatumomab and tyrosine kinase inhibitor

Introduction: Adults with relapsed or refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia (R/R Ph+ BCP-ALL) have a dismal outcome. Blinatumomab as a single agent has shown activity in R/R Ph- BCP-ALL, and second or third-generation tyrosine kinase inhibitors (TKIs) can produce high remission rates in Ph+ leukaemias. We aimed to assess the activity of blinatumomab and TKI in combination with intensive chemotherapy in the relapsed or refractory setting. Methods: Ten patients with R/R Ph+ BCP-ALL were treated with the combination of a modified hyper-CVAD (mHCVAD) regimen (cyclophosphamide, vincristine, adriamycin, dexamethasone), blinatumomab and TKI (mainly ponatinib). Results: Complete remission (CR) was achieved in 10/10 patients, with deep molecular responses, and 6/10 were alive in remission after a median follow-up of 19.4 months. Three major cardiovascular events were noted. Conclusion: These preliminary data, suggest that the mHCVAD-blinatumomab-TKI (mainly ponatinib) regimen may achieve a high rate of CR with undetectable measurable residual disease in adults with R/R Ph+ BCP-ALL and could be proposed to such patients, but cardiovascular or infectious complications should be warning, especially in older or frail patients.