Blinatumomab administered concurrently with oral tyrosine kinase inhibitor therapy is a well-tolerated consolidation strategy and eradicates measurable residual disease in adults with Philadelphia chromosome positive acute lymphoblastic leukemia

Abstract

Incorporation of ABL-targeted oral tyrosine kinase inhibitors (TKIs) into frontline therapeutic regimens has improved outcomes for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, patients with persistent minimal residual disease (MRD) exhibit increased risk of relapse. Combining consolidative chemotherapy with TKIs may increase rates of infectious complications, organ toxicity, hospitalization, and non-relapse mortality. Blinatumomab has demonstrated single-agent activity in patients with relapsed B-ALL or persistent MRD, including Ph + B-ALL. We have used blinatumomab concomitantly with commercially available TKIs as consolidative therapy to spare toxicities of conventional chemotherapy. We evaluated 11 adults with previously treated Ph + B-ALL who received blinatumomab concurrent with TKI (ponatinib, n = 5; dasatinib, n = 4; nilotinib, n = 1; imatinib, n = 1) to eradicate MRD or sustain MRD-negativity. Eight of 9 patients with MRD achieved BCR-ABL1 negativity (complete molecular response, CMR) after a median of one cycle; 2/2 patients without measurable disease durably maintained CMR. Cytokine release syndrome (all grade 1-2) was observed in 3/11 patients; one patient experienced transient grade 1 neurologic toxicity. Transient grade 2 transaminitis was observed in 6/11 patients, including 4/5 recipients of blinatumomab + ponatinib. This small series suggests blinatumomab + TKI is a safe and effective consolidation strategy for patients with Ph + ALL to achieve or maintain CMR.

Keywords: Acute lymphoblastic leukemia; Blinatumomab; Minimal residual disease; Tyrosine kinase inhibitor.