Blinatumomab Has Activity in Patients with TKI-Refractory Ph⁺ ALL

Approximately 25% of acute lymphoblastic leukemia (ALL) is Philadelphia chromosome–positive (Ph⁺), characterized by a reciprocal t(9;22) translocation that generates the chimeric BCR–ABL1 fusion protein and results in dysregulated tyrosine kinase activity. Treatment with tyrosine kinase inhibitors (TKI) is effective in the majority of patients with Ph⁺ ALL, but alternative approaches are needed to treat patients who relapse and develop resistance to TKIs. A previous phase II study showed that the bispecific T-cell engager antibody blinatumomab, which targets CD19-expressing B cells, was tolerable and exhibited antileukemia activity in patients with Ph⁻ ALL. In an open-label, single-arm, phase II study, Martinelli and colleagues evaluated the efficacy and tolerability of blinatumomab in 45 patients with Ph⁺ ALL who had progressed on TKI therapy. The primary endpoint was complete remission (CR) or CR with partial hematologic recovery (CRh). Secondary endpoints included minimal residual disease, rate of allogeneic hematopoietic stem-cell transplantation, relapse-free survival, overall survival, and adverse events. In total, 16 patients (36%) achieved a CR or CRh, including 4 of 10 patients with the BCR–ABL1^T315I mutation, a kinase domain mutation that confers resistance to TKIs. A complete minimal residual disease response was observed in 14 (88%) CR/CRh responders, and 7 (44%) responders proceeded to receive an allogeneic hematopoietic stem-cell transplant. The median relapse-free survival was 6.7 months and the median overall survival was 7.1 months. The most common adverse events were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Collectively, these findings indicate that blinatumomab has antileukemia activity as a single agent in patients with relapsed or refractory Ph⁺ ALL, supporting further clinical investigation of blinatumomab in patients with Ph⁺ disease.

Martinelli G, Boissel N, Chevallier P, Ottmann O, Gökbuget N, Topp MS, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol 2017 Mar 29 [Epub ahead of print].