In the open-label, phase III, TOWER trial, the CD3/CD19 bi-specific T-cell engaging (BiTE) antibody blinatumomab significantly improved overall survival (OS) and reduced risk of death by 29% compared to standard chemotherapy in patients with relapsed or refractory Philadelphia chromosome (Ph)-negative B cell precursor acute lymphoblastic leukemia (ALL).
In the TOWER trial, 405 patients were randomized to receive either blinatumomab (given in 6-week cycles of 4 weeks on and 2 weeks off) or investigator’s choice of one of four standard chemotherapy regimens. Patients in the blinatumomab arm with a high tumor burden received dexamethasone prior to treatment to prevent cytokine release syndrome. Blinatumomab treatment was associated with significant improvement in OS compared to chemotherapy (7.7 months vs 4.0 months; HR 0.71, P = .012), a benefit that was seen across all prespecified subgroups, including age, prior treatment, and prior allogeneic stem cell transplant.
Complete responses (CR) with full, partial, or incomplete hematologic recovery occurred in significantly more patients treated with blinatumomab (43.9% vs 24.6%; P<.001), and more patients in CR achieved minimal residual disease negativity with blinatumomab than with chemotherapy (76% vs 48%). The estimated 6-month event free survival rate was 30.7% with blinatumomab versus 12.5% with chemotherapy (HR 0.55, P<.001).
The safety profile of blinatumomab was consistent with previous studies. Patients treated with blinatumomab experienced fewer grade 3 and higher adverse events (AEs) than patients treated with chemotherapy (87% vs 92%). All grade ≥3 AEs of interest occurred more frequently in patients receiving chemotherapy, with the exception of cytokine release syndrome, which occurred in 5% of patients receiving blinatumomab.
The authors concluded that the high response rates and near doubling of OS confirm the preliminary analysis of blinatumomab efficacy and safety in relapsed/refractory patients with Ph-negative B cell precursor ALL, a high-risk population with historically poor outcomes. Blinatumomab received accelerated approval for this indication in November 2014 based on results from phase II data. Results from the TOWER trial support extension to full approval.