Long-term outcome of patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with blinatumomab

Abstract

Blinatumomab, the first-in-class CD3/CD19 bispecific T-cell engager antibody construct, has recently been approved for treating patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia. However, the clinical proof of concept of blinatumomab efficacy was initially demonstrated in patients with R/R B-cell non-Hodgkin lymphoma (B-NHL) in the MT103-104 phase 1 dose-escalation and expansion trial (NCT00274742), which defined 60 µg/m2 per day as the maximum tolerated dose (MTD). The clinically most relevant adverse effects were neurologic symptoms and cytokine release syndrome. Currently, there are no data on long-term outcomes and toxicity for B-NHL patients receiving blinatumomab treatment, so we performed a single-center, long-term follow-up analysis of 38 patients who participated in the MT103-104 phase 1 trial. We found no evidence for long-term toxicities, especially no blinatumomab-induced neurocognitive impairments. For the entire study population, the median overall survival (OS) was 4.6 years. Remarkably, patients who had received ≥60 µg/m2 per day and responded to blinatumomab achieved a median OS of 7.7 years. Of note, 6 of the surviving patients treated at the MTD have been treatment-free for more than 7 years. In contrast, patients who were treated at dose levels below the MTD had a median OS of only 1.1 years. These results indicate that 60 µg/m2 per day seems to represent the targeted dose level of blinatumomab required for durable remission in R/R B-NHL. Here, we provide the first clinical evidence that blinatumomab lacks long-term toxicity and has the potential to induce sustained remissions in patients with R/R B-NHL.

AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer

“…Bispecific T-cell engager (BiTE ® ) molecules are a clinically validated therapeutic modality that redirect a patient's T cells to kill tumor cells (15). Blinatumomab, the first BiTE ® molecule in clinical development, is approved for the treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia (16)(17)(18) and also demonstrates efficacy in non-Hodgkin lymphoma (19)(20)(21). The BiTE ® molecule AMG 420, which targets BCMA, demonstrated a 70% response rate in multiple myeloma with 50% minimal residual disease-negative complete responses at the maximum tolerated dose in a phase 1 study (22).…”

Durability of complete response after blinatumomab therapy for relapsed/refractory diffuse large B-cell lymphoma

“…Moreover, 3 patients in phase 2 R/R DLBCL study achieved late CRs that were not captured in this pooled analysis and had longer DOCRs [5]. Furthermore, in a subset of patients with R/R B-NHL from phase 1 study (NCT00274742), remission is ongoing after more than 7 years [10]. There was no difference between CR and non-CR patients in rate of prior transplant or double hit disease.…”

Emerging therapies in mantle cell lymphoma

“…The most advanced BiTe in clinical development for B cell malignancies is blinatumomab, an antibody that crosslinks B cells and T cells by ligating CD3 and CD19. In phase I trial of relapsed/refractory NHL (n = 76), blinatumomab demonstrated an ORR of 69% and a CR rate of 37% [95] with durable responses in some patients on long-term follow-up [96]. Of note, patients with relapsed/refractory MCL (n = 24) had a higher ORR compared to DLBCL (71% versus 55%, respectively) [95].…”