Blinatumomab Treatment in Adult Patients with Relapsed/Refractory Ph+ ALL: Results from the Phase 2 ALCANTARA Trial
Despite the incorporation of tyrosine kinase inhibitors (TKIs) into treatment regimens, patients with relapsed/refractory Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) have a poor prognosis, underscoring the need for novel treatment strategies. Blinatumomab is a bispecific T-cell engaging (BiTE®) CD19-directed antibody construct that has shown antileukemic activity in adult patients with relapsed/refractory Ph-negative ALL, with a 43% complete remission (CR)/CR with partial hematologic recovery (CRh) rate during the first 2 cycles.1 The multicenter phase 2 ALCANTARA trial evaluated the efficacy and tolerability of blinatumomab in 45 patients with relapsed/refractory Ph+ ALL who progressed after or were intolerant to a second or later (2+) generation TKI; the results of this trial were reported by Martinelli and colleagues.2
In this trial, blinatumomab (9 ?g/day on days 1-7 in cycle 1, and 28 ?g/day thereafter) was administered by continuous intravenous infusion (4 weeks on/2 weeks off) for up to 5 cycles; the primary end point was CR or CRh during the first 2 cycles. In the study population (n = 45), 60% of patients had received ?2 prior 2+ generation TKIs, 38% of patients had ?2 prior relapses, 44% had undergone allogeneic hematopoietic stem-cell transplantation, and 27% of patients had a BCR-ABL gene with T315I mutation. Overall, 16 (36%) patients achieved CR/CRh during the first 2 cycles; of these, 14 patients also achieved a complete minimal residual disease (MRD) response. Patients with the difficult-to-treat T315I mutations also achieved responses—4 of the 10 achieved CR/CRh and complete MRD responses. At a median follow-up of approximately 9 months, median relapse-free survival was 6.7 months and median overall survival was 7.1 months. Grade ?3 treatment-emergent adverse events (AEs) occurred in 82% of patients, including febrile neutropenia (27%), thrombocytopenia (22%), anemia (16%), and pyrexia (11%). Five deaths were reported due to AEs, including 1 due to septic shock that was deemed treatment-related. Cytokine release syndrome was reported in 3 (7%) patients, 21 (47%) patients had neurologic events, 3 of which were grade 3, including aphasia, hemiplegia; and depressed level of consciousness and nervous system disorder. Based on these results, the authors concluded that single-agent blinatumomab immunotherapy in poor prognosis patients with relapsed/refractory Ph+ ALL was associated with promising antileukemic activity and a safety profile that was consistent with those previously described in Ph-negative ALL.
- Topp MS, et al. Lancet Oncol. 2015;16:57-66.
- Martinelli G, et al. ASH 2015. Abstract 679.