TY  - JOUR
A1  - Einsele, Hermann
A1  - Borghaei, Hossein
A1  - Orlowski, Robert Z.
A1  - Subklewe, Marion
A1  - Roboz, Gail J.
A1  - Zugmaier, Gerhard
A1  - Kufer, Peter
A1  - Iskander, Karim
A1  - Kantarjian, Hagop M.
T1  - The BiTE (Bispecific T‐Cell Engager) Platform: Development and Future Potential of a Targeted Immuno‐Oncology Therapy Across Tumor Types
JF  - Cancer
N2  - Immuno‐oncology therapies engage the immune system to treat cancer. BiTE (bispecific T‐cell engager) technology is a targeted immuno‐oncology platform that connects patients' own T cells to malignant cells. The modular nature of BiTE technology facilitates the generation of molecules against tumor‐specific antigens, allowing off‐the‐shelf immuno‐oncotherapy. Blinatumomab was the first approved canonical BiTE molecule and targets CD19 surface antigens on B cells, making blinatumomab largely independent of genetic alterations or intracellular escape mechanisms. Additional BiTE molecules in development target other hematologic malignancies (eg, multiple myeloma, acute myeloid leukemia, and B‐cell non‐Hodgkin lymphoma) and solid tumors (eg, prostate cancer, glioblastoma, gastric cancer, and small‐cell lung cancer). BiTE molecules with an extended half‐life relative to the canonical BiTE molecules are also being developed. Advances in immuno‐oncology made with BiTE technology could substantially improve the treatment of hematologic and solid tumors and offer enhanced activity in combination with other treatments.
KW  - B cell
KW  - blinatumomab
KW  - hematologic malignancies
KW  - T cell
KW  - tumor‐specific antigen
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215426
VL  - 126
IS  - 14
SP  - 3192
EP  - 3201
ER  - 
TY  - JOUR
A1  - Stein, Anthony S.
A1  - Kantarjian, Hagop
A1  - Gökbuget, Nicola
A1  - Bargou, Ralf
A1  - Litzow, Mark R.
A1  - Rambaldi, Alessandro
A1  - Ribera, Josep-Maria
A1  - Zhang, Alicia
A1  - Zimmerman, Zachary
A1  - Zugmaier, Gerhard
A1  - Topp, Max S.
T1  - Blinatumomab for Acute Lymphoblastic Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation
JF  - Biology of Blood and Marrow Transplantation
N2  - Patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) following allogeneic hematopoietic stem cell transplantation (alloHSCT) have a poor prognosis, and alternative therapies are needed for this patient population. Blinatumomab, a bispecific T cell engager immunotherapy, was evaluated in an open-label, single-arm, phase II study of adults with R/R Philadelphia chromosome-negative B cell precursor ALL and resulted in a rate of complete remission (CR) or CR with partial hematologic recovery of peripheral blood counts (CRh) of 43% within 2 treatment cycles. We conducted an exploratory analysis to determine the efficacy and safety of blinatumomab in 64 patients who had relapsed following alloHSCT before enrollment in the phase II study. Forty-five percent of the patients (29 of 64) achieved a CR/CRh within the first 2 cycles of treatment, 22 of whom had a minimal residual disease (MRD) response (including 19 with a complete MRD response). After 1 year and 3 years of follow-up, the median relapse-free survival was 7.4 months for patients who achieved CR/CRh in the first 2 cycles, and the median overall survival was 8.5 months; overall survival rate (Kaplan-Meier estimate) was 36% at 1 year and 18% at 3 years. Grade 3 and 4 adverse events were reported in 20 patients (31%) and 28 patients (44%), respectively, with grade 3 and 4 neurologic events in 8 and 2 patients, respectively, and grade 3 cytokine release syndrome in 2 patients. Eight patients had fatal adverse events, including 5 due to infections. Seven patients had grade ≤ 3 graft-versus-host disease during the study, none of which resulted in the discontinuation of blinatumomab or hospitalization. Our data suggest that blinatumomab is an effective salvage therapy in this patient population.
KW  - blinatumomab
KW  - Philadelphia chromosome-negative B precursor ALL
KW  - efficacy
KW  - safety
KW  - allogeneic hematopoietic stem cell transplantation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239510
VL  - 25
ER  -