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Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia

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TLDR
Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B‐cell precursor ALL, and remission rates within 12 weeks after treatment initiation were significantly higher.
Abstract
BackgroundBlinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. MethodsIn this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standard-of-care chemotherapy. The primary end point was overall survival. ResultsOf the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab...

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Citations
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Journal ArticleDOI

Infectious complications of CD19-targeted chimeric antigen receptor–modified T-cell immunotherapy

TL;DR: Cytokine release syndrome (CRS) severity was the only factor after CAR-T-cell infusion associated with infection in a multivariable analysis and the incidence of infections was comparable to observations from clinical trials of salvage chemoimmunotherapies in similar patients.
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Oncolytic viruses as engineering platforms for combination immunotherapy.

TL;DR: It is argued that the future of immunotherapy will include OVs that function as multiplexed immune-modulating platforms expressing factors such as immune checkpoint inhibitors, tumour antigens, cytokines and T cell engagers with the potential to improve the effectiveness of immunotherapies through novel synergistic mechanisms promoting antitumour immune activity.
Journal ArticleDOI

Acute lymphoblastic leukaemia

TL;DR: New immunotherapeutic strategies, such as monoclonal antibodies and chimeric antigen receptor (CAR) T cells, are being developed and over the next few years could change the options for acute lymphoblastic leukaemia treatment.
Journal ArticleDOI

A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403.

TL;DR: Use of a pediatric regimen for AYA patients with newly diagnosed ALL up to age 40 years was feasible and effective, resulting in improved survival rates compared with historical controls, and CALGB 10403 can be considered a new treatment standard upon which to build for improving survival for AYAs with ALL.
Journal ArticleDOI

T cell-engaging therapies - BiTEs and beyond.

TL;DR: The authors review the clinical results obtained with bispecific antibodies to date and discuss the challenges associated with this therapeutic approach and the proposed solutions aimed at preventing or minimizing toxicities, countering immune escape and broadening the indications for these treatments.
References
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Journal ArticleDOI

Chimeric antigen receptor T cells for sustained remissions in leukemia.

TL;DR: Chimeric antigen receptor-modified T-cell therapy against CD19 was effective in treating relapsed and refractory ALL and was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed.
Journal ArticleDOI

A multiple testing procedure for clinical trials.

TL;DR: The overall size of the procedure is shown to be controlled with virtually the same accuracy as the single sample chi-square test based on N(m1 + m2) observations and the power is found to bevirtually the same.
Journal ArticleDOI

Discrete sequential boundaries for clinical trials

K. K. Gordon Lan, +1 more
- 01 Dec 1983 - 
TL;DR: In this article, the authors proposed a more flexible method to construct discrete sequential boundaries based on the choice of a function, a*(t), which characterizes the rate at which the error level ac is spent.
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