Potential for bispecific T-cell engagers: role of blinatumomab in acute lymphoblastic leukemia

Figures & data

Figure 1 Generation, structure, and mode of action of blinatumomab.

Notes: (A) Variable domains (V_H and V_L) of a CD19-specific monoclonal antibody and a CD3-specific monoclonal antibody were converted into single-chain antibodies recombinantly joined by nonimmunogenic linker sequences; (B) cell lysis by blinatumomab involves toxic proteins that are normally stored inside secretory vesicles of cytotoxic T-cells and are discharged when the BiTE antibody forces formation of a cytolytic synapse between T-cells and leukemic cells.
Abbreviation: BiTE, bi-specific T-cell engager.

Table 1 Clinical trials with blinatumomab currently recruiting

Clinical trial identifier	Phase	Condition	Drugs	Primary end points
NCT 02412306 (Horai study)	I/II	R/R ALL, Ph^− (all ages)	Blinatumomab	Phase I: DLT, Phase II: CR/CRh
NCT 02393859	III	First relapse, Ph^− (≤17 years)	Blinatumomab vs conventional chemo	EFS
NCT 02458014	II	MRD-positive ALL	Blinatumomab	RFS
NCT 02143414	II	Newly diagnosed ALL (Ph^+ included) (≥65 years)	Blinatumomab plus chemo ± dasatinib	OS, DLT
NCT 02101853	III	First relapse, Ph^− (1–30 years)	Blinatumomab vs conventional chemo	DFS
NCT 02003222	III	Newly diagnosed ALL, Ph^− (adults)	Blinatumomab plus chemo vs chemo alone	OS
NCT 02187354 (RIALTO)	ND	R/R ALL (including after allo HSCT), Ph^− (≤17 years)	Blinatumomab	AEs

Abbreviations: AEs, adverse events; ALL, acute lymphoblastic leukemia; allo HSCT, allogeneic hematopoietic stem cell transplantation; chemo, chemotherapy; CR/CRh, complete response/complete remission with partial hematological recovery; DFS, disease-free survival; DLT, dose-limiting toxicity; EFS, event-free survival; MRD, minimal residual disease; ND, not done; OS, overall survival; Ph, Philadelphia chromosome; RFS, relapse-free survival; R/R, relapsed/refractory.

Table 2 Adverse events (grade ≥3) regardless of causality

Adverse events	Topp et al^Citation50 (21 patients)	Topp et al^Citation53,Citation54 (189 patients)
Peripheral blood
Leukopenia	2 (9.5%)	15 (7.9%)
Neutropenia	1 (4.8%)	30 (15.8%)
Thrombopenia	1 (4.8%)	16 (8.4%)
Investigations
ALT increased	1 (4.8%)	13 (6.8%)
Ig decreased	5 (23.8%)	ND
Infections
Bacterial sepsis	1 (4.8%)	15 (7.9%)
Bronchopneumonia	1 (4.8%)	17 (8.9%)
Neurologic events
Syncope/convulsion	1 (4.8%)	2 (1%)
Encephalopathy	ND	6 (3.1%)
Somnolence	1 (4.8%)	1 (<1%)
Metabolism disorders
Hypokalemia	1 (4.8%)	13 (6.8%)
Hypophosphatemia	ND	10 (5.2%)

Abbreviations: ALT, alanine aminotransferase; Ig, immunoglobulin; ND, not done.

ToppMSKuferPGökbugetNTargeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survivalJ Clin Oncol201129182493249821576633

 PubMed Web of Science ®Google Scholar

ToppMSGökbugetNZugmaierGPhase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemiaJ Clin Oncol201432364134414025385737

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ToppMSGökbugetNSteinASSafety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 studyLancet Oncol2015161576625524800

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