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Background Global studies have demonstrated the efficacy and safety of blinatumomab-a BiTE® (bispecific T-cell engager) targeted immuno-oncology therapy that mediates the lysis of cells expressing CD19 in patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL). Because limited data are available in Asian patients, we conducted a post hoc pooled analysis in 45 Asian adult patients with R/R ALL-19 from the blinatumomab arm of TOWER (NCT02013167) and 26 from Study 265, a phase 1b/2 study in Japanese adults (NCT02412306). Methods Patients received a maximum of two cycles of induction blinatumomab for 4 weeks by continuous intravenous infusion (cycle 1/week 1: 9 μg/day; cycle 1/weeks 2-4: 28 μg/day) followed by 2 weeks of no blinatumomab (each 6-week cycle); patients received 28 μg/day blinatumomab in subsequent cycles. Results Twenty of 45 patients enrolled (44%) achieved complete remission with full or partial hematologic recovery compared with 44% in TOWER and 80% and 38% in phase 1b and phase 2, respectively, of Study 265. The Kaplan-Meier (KM) median overall survival was 11.9 months (95% confidence interval [CI], 9.9-17.1) and the KM median duration of relapse-free survival was 8.9 months (95% CI, 3.8-10.7). Ninety-three percent of patients had grade ≥ 3 treatment-emergent adverse events (AEs) compared with 87% in TOWER and 80% and 100% in phase 1b and phase 2, respectively, of Study 265. Five patients (11.4%) had fatal AEs. Conclusions The safety and efficacy of blinatumomab in Asian patients were comparable with those reported in previous global studies with no new safety signals.

Adult patients with relapsed/refractory (R/R) B‐precursor acute lymphoblastic leukemia (ALL) have a poor prognosis. Blinatumomab is a bispecific T‐cell engager (BiTE) immuno‐oncology therapy with dual specificity for CD19 and CD3 that redirects patients’ CD3‐positive cytotoxic T cells to lyse malignant and normal B cells. We conducted an open‐label, phase 1b/2 study to determine the safety, pharmacokinetics, efficacy and recommended dose of blinatumomab in Japanese adults with R/R B‐precursor ALL. Patients received 9 μg/day blinatumomab during week 1 and 28 μg/day during weeks 2‐4, with a 2‐week treatment‐free interval (6‐week cycle); patients received 28 μg/day blinatumomab in subsequent cycles. Primary endpoints were the incidence of dose‐limiting toxicities (DLT) in phase 1b and complete remission (CR)/CR with partial hematologic recovery (CRh) within the first two cycles in phase 2. A total of 26 patients enrolled and 25 (96%) reported grade ≥3 adverse events (mostly cytopenias). There were no DLT. CR/CRh within two cycles was achieved by 4 of 5 patients (80%) in phase 1b and 8 of 21 patients (38%) in phase 2. Among patients with evaluable minimal residual disease, 4 (100%) in phase 1b and 3 (38%) in phase 2 had a complete MRD response. Median RFS for 8 patients who achieved CR/CRh in phase 2 was 5 (95% CI: 3.5‐6.4) months; median OS was not estimable. There were no significant associations between maximum cytokine levels or percentage of specific cell types during cycle 1 and response. Consistent with global studies, blinatumomab appeared to be safe and efficacious in Japanese adults with R/R ALL., Flow of patients through the study. (A) Phase 1b part. (B) Phase 2 part.

Twenty adult patients with high-risk leukaemia underwent allogeneic haemopoietic stem cell transplantation after melphalan, busulphan and total body irradiation followed by short-term methotrexate and low-dose cyclosporine or tacrolimus. Three patients developed veno-occlusive disease and no patient developed renal dysfunction. Seven patients experienced grade II-IV acute graft-versus-host disease (aGVHD) and five patients experienced grade III-IV. The 3-year probabilities of relapse and leukaemia-free survival were 22 +/- 11% (95% confidence interval) and 50 +/- 11%, respectively. These data suggest that this preconditioning regimen followed by a low-dose immunosuppressant provided a more anti-leukaemic effect without increased regimen-related toxicity and aGVHD.