The prognosis of adult patients with relapsed and/or refractory acute lymphoblastic leukemia (ALL) who have had prior allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is poor, underscoring the need for novel therapeutic options. Blinatumomab is a bispecific T-cell engaging (BiTE®) CD19-directed antibody construct that has shown antileukemia activity in a large confirmatory open-label, single-arm, phase 2 study in patients with Philadelphia chromosome–negative relapsed/refractory ALL.1 This analysis sought to characterize the subset of patients with relapsed/refractory ALL in this trial who had undergone allo-HSCT prior to blinatumomab therapy.2 A total of 189 patients were enrolled and received blinatumomab by continuous intravenous infusion (4 weeks on/2 weeks off) for up to 5 cycles. Of these, 64 (34%) patients had undergone allo-HSCT prior to blinatumomab treatment. The median age of this patient subset with prior allo-HSCT was 32 years, and 28 (44%) patients had relapsed post–allo-HSCT. Donor types included matched sibling (45%) or unrelated (48%); 34 patients (59%) received myeloablative conditioning regimens. The majority (69%) of patients had received salvage therapy after last allo-HSCT and prior to blinatumomab treatment, with 50% of patients having received ?3 prior salvage therapies. Median time from last allo-HSCT and subsequent relapse was 6 months; median time from last prior allo-HSCT to first dose of blinatumomab was 10 months. Overall, 45% of patients with prior allo-HSCT achieved a complete remission (CR; n = 18)/CR with partial hematologic recovery (CRh; n = 11) within the first 2 cycles, which was comparable to the CR/CRh rate achieved by the allo-HSCT–naïve (42%) cohort. Of the 18 complete responders, 16 (89%) achieved a minimal residual disease (MRD) response; 15 (83%) were complete MRD responses. Moreover, 7 (24%) responders subsequently underwent an allo-HSCT. At a median follow-up of 16.6 months, median overall survival (OS) was 8.5 months in the cohort with prior allo-HSCT treated with blinatumomab; median relapse-free survival (RFS) was 7.4 months at a median follow-up of 12.4 months. Overall, 56 (88%) patients experienced grade ?3 treatment-emergent adverse events (AEs), including neutropenia (22%), febrile neutropenia (20%), anemia (17%), and thrombocytopenia (14%). Grade 3 neurologic events occurred in 11% of patients and grade 3 cytokine release syndrome in 3% of patients. Treatment-emergent graft-versus-host disease was reported in 7 patients during blinatumomab treatment. Seven deaths due to treatment-emergent AEs were reported, including 1 due to gastrointestinal hemorrhage, 1 due to respiratory failure, and 5 due to infection. Based on these results, it was concluded that blinatumomab therapy was equally effective in inducing remission rates in patients who had relapsed on prior allo-HSCT as well as in those who were allo-HSCT–naïve, and showed an AE profile that was consistent with that previously described.
