scholarly journals Concepts in immuno-oncology: tackling B cell malignancies with CD19-directed bispecific T cell engager therapies

2020 ◽  
Vol 99 (10) ◽  
pp. 2215-2229
Author(s):  
Andreas Viardot ◽  
Franco Locatelli ◽  
Julia Stieglmaier ◽  
Faraz Zaman ◽  
Elias Jabbour
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor ◽  
B Cell Malignancies ◽  
T Cell Therapy ◽  
Bispecific T Cell Engager

Abstract The B cell surface antigen CD19 is a target for treating B cell malignancies, such as B cell precursor acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma. The BiTE® immuno-oncology platform includes blinatumomab, which is approved for relapsed/refractory B cell precursor acute lymphoblastic leukemia and B cell precursor acute lymphoblastic leukemia with minimal residual disease. Blinatumomab is also being evaluated in combination with other agents (tyrosine kinase inhibitors, checkpoint inhibitors, and chemotherapy) in various treatment settings, including frontline protocols. An extended half-life BiTE molecule is also under investigation. Patients receiving blinatumomab may experience cytokine release syndrome and neurotoxicity; however, these events may be less frequent and severe than in patients receiving other CD19-targeted immunotherapies, such as chimeric antigen receptor T cell therapy. We review BiTE technology for treating malignancies that express CD19, analyzing the benefits and limitations of this bispecific T cell engager platform from clinical experience with blinatumomab.

A Systematic Review of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Engaging an Old Problem With New Solutions

2021 ◽  
pp. 106002802098841
Author(s):  
Zachery Halford ◽  
Carli Coalter ◽  
Vanessa Gresham ◽  
Tabitha Brown
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Phase Iii ◽  
Cytotoxic T Cell ◽  
Bispecific T Cell Engager

Objective: To assess the current literature for blinatumomab in the treatment of adult and pediatric B-cell acute lymphoblastic leukemia (ALL). Data Sources: We conducted a PubMed (inception to December 11, 2020) and ClinicalTrials.gov systematic literature search using the following terms: blinatumomab, Blincyto, lymphoblastic leukemia, and bispecific T-cell engager. Study Selection and Data Extraction: All relevant published articles, package inserts, and meeting abstracts evaluating the use of blinatumomab in ALL were considered for inclusion. Data Synthesis: Blinatumomab, a first-in-class bispecific T-cell engager monoclonal antibody, facilitates cytotoxic T-cell activation and subsequent eradication of CD19-positive B cells. The confirmatory phase III TOWER trial demonstrated superior overall survival (OS) with blinatumomab compared with standard chemotherapy (7.7 months vs 4.0 months) in relapsed and refractory (R/R) B-cell ALL. In the phase II BLAST trial, blinatumomab achieved a complete measurable residual disease (MRD) response in 78% of evaluable patients, with a median OS of 36.5 months. Potentially life-threatening cytokine release syndrome and neurotoxicity occurred in approximately 15% and 65% of patients, respectively. Relevance to Patient Care and Clinical Practice: Following initial Food and Drug Administration approval in 2014, blinatumomab gained expanded approval in pediatric patients and in Philadelphia chromosome-positive R/R ALL. In 2018, blinatumomab became the first and only drug approved for the treatment of persistent MRD in any hematologic malignancy. Emerging data demonstrate promising efficacy with blinatumomab in specific ALL settings, including frontline therapy, as a bridge to transplantation, and in “chemotherapy-free” combination regimens. Conclusions: Blinatumomab provides a paradigm-shifting treatment option; however, many questions surrounding optimal patient selection, sequencing, and cost-effectiveness remain.

scholarly journals Bispecific T-cell engaging antibodies in B-cell precursor acute lymphoblastic leukemias: focus on blinatumomab

2020 ◽  
Vol 11 ◽  
pp. 204062072091963
Author(s):  
Jose-Maria Ribera ◽  
Eulalia Genescà ◽  
Jordi Ribera
Keyword(s):  
T Cell ◽  
B Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Development Program ◽  
Cell Transplant ◽  
Cell Precursor ◽  
Hematopoietic Stem ◽  
Clinical Development Program

Bispecific T-cell engaging antibodies are constructs engineered to bind to two different antigens, one to a tumor-specific target and the other to CD3-positive T cells or natural killer (NK) cells. Blinatumomab engages CD19 and CD3, performing effective serial lysis. The clinical development program in acute lymphoblastic leukemia (ALL) includes clinical trials in relapsed or refractory (R/R) patients and in B-cell precursor (BCP) ALL patients with measurable residual disease. Several trials are currently being conducted in de novo BCP-ALL, either in induction, consolidation, or before or after hematopoietic stem cell transplant. Combination with other targeted therapies or with other immunotherapeutic approaches are also underway. Several strategies are aimed to optimize the use of blinatumomab either by overcoming the mechanisms of resistance (e.g. inhibition of PD-1/PD-L1) or by improvements in the route of application, among others.

scholarly journals Recent updates for antibody therapy for acute lymphoblastic leukemia

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Le Li ◽  
Ying Wang
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Complete Remission ◽  
Median Survival ◽  
Residual Disease ◽  
Hematologic Malignancy ◽  
Lymphoblastic Leukemia ◽  
Cytotoxic Agents ◽  
Great Promise ◽  
T Cell Therapy

AbstractAcute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Current immunotherapies exploit the performance of antibodies through several different mechanisms, including naked antibodies, antibodies linked to cytotoxic agents, and T-cell re-directing antibodies. Compared with chemotherapy, the application of an antibody–drug conjugates (ADC) called inotuzumab ozogamicin in relapsed or refractory (R/R) CD22+. ALL resulted in a complete remission (CR) rate of 81% and an overall median survival of 7.7 months with reduced toxicity. Similarly, blinatumomab, the first FDA-approved bispecific antibody (BsAb), produced a 44% complete response rate and an overall median survival of 7.7 months in a widely treated ALL population. In addition, approximately 80% of patients getting complete remission with evidence of minimal residual disease (MRD) achieved a complete MRD response with the use of blinatumomab. These results highlight the great promise of antibody-based therapy for ALL. How to reasonably determine the place of antibody drugs in the treatment of ALL remains a major problem to be solved for ongoing and future researches. Meanwhile the combination of antibody-based therapy with traditional standard of care (SOC) chemotherapy, chimeric antigen receptor (CAR) T-cell therapy and HSCT is also a challenge. Here, we will review some important milestones of antibody-based therapies, including combinational strategies, and antibodies under clinical development for ALL.

scholarly journals CAR-T Cell Therapy

2020 ◽  
Vol 21 (12) ◽  
pp. 4303
Author(s):  
Aamir Ahmad
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Hematological Malignancies ◽  
Lymphoblastic Leukemia ◽  
T Cell Therapy ◽  
Car T Cell Therapy ◽  
Car T ◽  
Large B Cell

CAR-T therapy has revolutionized the treatment of select hematological malignancies, namely, acute lymphoblastic leukemia and large B-cell lymphomas [...]

scholarly journals Curative outcomes following blinatumomab in adults with minimal residual disease B-cell precursor acute lymphoblastic leukemia

2020 ◽  
Vol 61 (11) ◽  
pp. 2665-2673 ◽  
Author(s):  
Nicola Gökbuget ◽  
Gerhard Zugmaier ◽  
Hervé Dombret ◽  
Anthony Stein ◽  
Massimiliano Bonifacio ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor ◽  
Minimal Residual
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