Bispecific T-Cell Engager Antibody Construct Blinatumomab Shows Durable Response in a Long-Term Follow-up Analysis of 38 NHL Patients Treated in a Phase I Trial

Introduction: Treatment of relapsed/refractory (rr) Non-Hodgkinxs lymphoma of B-cell type (B-NHL) is still challenging and new and more effective therapies are urgently warranted. Blinatumomab, a bispecific T-cell engager (BiTE^®) antibody construct, engages CD3⁺ cytotoxic T cells, resulting in T-cell expansion and lysis of CD19⁺ B cells.  In a prior phase I study, blinatumomab treatment resulted in an overall response rate (ORR) of 69% and 55% in diffuse large B-cell lymphoma (DLBCL), respectively for patients treated at 60 μg/m²/d. Based on this study we here present a single-center analysis on long-term outcome of patients with B-NHL after treatment with blinatumomab. We here report first preliminary data on long-term follow-up of patients with rr NHL after blinatumomab treatment.

Methods: Patients with rr B-NHL who achieved an objective response (PR or CR) upon blinatumomab treatment were eligible for long-term follow-up analysis. Kaplan-Meier estimates for progression free survival (PFS) probability were calculated from first infusion to relapse or death. Patients without an event were censored at last follow-up. This study was conducted in accordance with the Declaration of Helsinki.

Results: Out of 38 treated patients (17 follicular lymphoma (FL), 14 mantle cell lymphoma (MCL), 4 DLBCL, 3 others) 22 received the effective target dose of 60/90 μg/m²/d. 47,4% (CR/PR=28,9%/18,4%, n=38) and 68,2% (CR/PR=40,9%/27,3%, n=22) of the patients experienced response, respectively, whereas only 18,8% of the patients who were not treated with the effective target dose responded to blinatumomab (CR/PR=12,5%/6,3%, n=16). 6 patients are still in ongoing remission.

Figure1: Kaplan Meier analysis shows significantly longer PFS in patients on target dose

Median overall survival (OS) of all 38 patients was 1560 days, median PFS 204 days and treatment free survival (TFS) 233 days. Median OS in the 22 patients treated with the target dose was 1793 days, median PFS 492 and TFS 752 days, compared to only 412 days median OS, 46 days PFS and 82 days TFS in the patients, who did not receive blinatumomab in an effective dosage.

Conclusion: Blinatumomab has the potential to induce durable remissions in patients with rr NHL. Our data suggests that treatment at target dose of 60 μg/m²/d is an important prerequisite to achieve long-term remission.