A review of blinatumomab, a novel immunotherapy

Abstract

Blinatumomab is a novel bispecific CD19-directed CD3 T-cell engager recently approved for the treatment of relapsed or refractory Ph-negative acute lymphoblastic leukemia in adults. The drug was approved after a phase II trial in adults with relapsed/refractory disease demonstrated complete remission or hematologic complete remission in 43% of patients within two treatment cycles, of which 40% went on to receive an allogeneic hematopoietic stem cell transplant. In a long-term survival analysis of patients with minimal residual disease after chemotherapy, hematologic relapse-free survival was estimated at 61% at a median of 33 months after blinatumomab. Nine patients underwent hematopoietic stem cell transplant, and six patients remained in complete remission without hematopoietic stem cell transplant or further therapy. Limited data in relapsed pediatric acute lymphoblastic leukemia are reviewed. Blinatumomab carries boxed warnings for neurotoxicity and cytokine release syndrome, which may be serious and lead to treatment interruption and discontinuation. Clinical controversies with blinatumomab include use in patients with Ph-positive acute lymphoblastic leukemia, dosing in underweight adults, and the optimal management of cytokine release syndrome. Oncology pharmacists must be aware of detailed preparation and administration procedures required for safe use of blinatumomab. Clinical trials are ongoing in the first-line setting for patients with Ph-negative acute lymphoblastic leukemia, in Ph-positive acute lymphoblastic leukemia, and other B-cell malignancies.

Therapeutic potential of SGN-CD19B, a PBD-based anti-CD19 drug conjugate, for treatment of B-cell malignancies

“…27 Blinatumomab shows reasonable activity in relapsed/ refractory B-NHL, 26 yet the requirement for continuous infusion and associated neurologic toxicities are notable drawbacks. 28,29 CD19-directed CAR-T cell therapies have demonstrated promising responses in B-cell malignancies 30 and will likely have a place in the future; however, technical challenges in manufacturing may limit their broad applicability to all relapsed/refractory patients. [31][32][33] Here we describe the preclinical evaluation of SGN-CD19B and highlight notable features that distinguish it from other ADCs in development for B-NHL and B-ALL.…”

Mono- and dual-targeting triplebodies activate natural killer cells and have anti-tumor activityin vitroandin vivoagainst chronic lymphocytic leukemia

“…CD19, a 95 kDa transmembrane glycoprotein, is an attractive and a clinically validated target for antibody-derived therapeutic agents against malignant B cells such as CLL. [31][32][33][34] It is exclusively expressed on all developmental stages of B cells except on terminally differentiated plasma cells and unlike CD20 is not shed from the cell surface upon treatment. 31,32 A CD19-specific triplebody in a single polypeptide format targeting CD16 receptor on effector cells was previously developed.…”

Bispecific antibodies in cancer immunotherapy

“…Currently, 2 bispecific antibodies, catumaxomab (anti-EpCAM and anti-CD3) and blinatumomab (anti-CD19 and anti-CD3), have been approved for patient care and have made a substantial impact on both research and the development of biologics. [7][8][9] Many more diverse formats for bispecific antibodies are now in transit from the bench to bedside (Table 1). This review is focused on bispecific antibodies that recruit immune cells for cancer therapy, which was first demonstrated in vitro 30 y ago.…”

“…62 The BiTE antibody blinatumomab (AMG 103, MT103) is approved by the US Food and Drug Administration for treatment of patients with Philadelphia chromosome-negative precursor Bcell acute lymphoblastic leukemia (B-ALL). 8,9 Blinatumomab is composed of 2 scFvs, one targeting CD19 and one against CD3, with equilibrium dissociation constants (K D ) of 10 ¡9 and 10 ¡7 M, respectively. 66 After engagement of T cells via the anti-CD3 domain, blinatumomab creates a structural immune synapse with CD19 C cells, 68 leading to T-cell activation and cytotoxicity toward CD19 C cells.…”