The social value of tisagenlecleucel, a CAR-T cell therapy, for the treatment of relapsed or refractory pediatric acute lymphoblastic leukemia in the United States: What are consequences of treatment delays?

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 10529-10529 ◽  
Author(s):  
Julia Thornton Snider ◽  
Michelle Brauer ◽  
Katharine Batt ◽  
Pinar Karaca-Mandic ◽  
Jie Zhang ◽  
...  
Keyword(s):  
United States ◽  
Lymphoblastic Leukemia ◽  
The United States ◽  
Social Value ◽  
T Cell Therapy ◽  
Treatment Delays ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Car T Cell Therapy ◽  
The Social ◽  
Car T

Value and affordability of CAR T-cell therapy in the United States

2020 ◽  
Vol 55 (9) ◽  
pp. 1706-1715 ◽  
Author(s):  
Salvatore Fiorenza ◽  
David S. Ritchie ◽  
Scott D. Ramsey ◽  
Cameron J. Turtle ◽  
Joshua A. Roth
Keyword(s):  
United States ◽  
T Cell ◽  
Cell Therapy ◽  
The United States ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals The landscape of CAR T‐cell therapy in the United States and China: A comparative analysis

2018 ◽  
Vol 144 (8) ◽  
pp. 2043-2050 ◽  
Author(s):  
Lijuan Gou ◽  
Jianchao Gao ◽  
Huan Yang ◽  
Chenyan Gao
Keyword(s):  
United States ◽  
Comparative Analysis ◽  
T Cell ◽  
Cell Therapy ◽  
The United States ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Identification of Cell Populations Associated with CD19Neg Relapse Following CAR T Cell Therapy in Acute Lymphoblastic Leukemia

2021 ◽  
Vol 27 (3) ◽  
pp. S74
Author(s):  
Pablo Domizi ◽  
Astraea Jager ◽  
Jolanda Sarno ◽  
Charles G. Mullighan ◽  
Stephan Grupp ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
Lymphoblastic Leukemia ◽  
Cell Populations ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Single-cell profiling identifies pre-existing CD19-negative subclones in a B-ALL patient with CD19-negative relapse after CAR-T therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tracy Rabilloud ◽  
Delphine Potier ◽  
Saran Pankaew ◽  
Mathis Nozais ◽  
Marie Loosveld ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
T Cell ◽  
Single Cell ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
T Cell Therapy ◽  
Car T Cell Therapy ◽  
Car T ◽  
Single Cell Profiling

AbstractChimeric antigen receptor T cell (CAR-T) targeting the CD19 antigen represents an innovative therapeutic approach to improve the outcome of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Yet, despite a high initial remission rate, CAR-T therapy ultimately fails for some patients. Notably, around half of relapsing patients develop CD19 negative (CD19neg) B-ALL allowing leukemic cells to evade CD19-targeted therapy. Herein, we investigate leukemic cells of a relapsing B-ALL patient, at two-time points: before (T1) and after (T2) anti-CD19 CAR-T treatment. We show that at T2, the B-ALL relapse is CD19 negative due to the expression of a non-functional CD19 transcript retaining intron 2. Then, using single-cell RNA sequencing (scRNAseq) approach, we demonstrate that CD19neg leukemic cells were present before CAR-T cell therapy and thus that the relapse results from the selection of these rare CD19neg B-ALL clones. In conclusion, our study shows that scRNAseq profiling can reveal pre-existing CD19neg subclones, raising the possibility to assess the risk of targeted therapy failure.

scholarly journals KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results

Blood ◽  
2021 ◽  
Author(s):  
Bijal D Shah ◽  
Michael R. Bishop ◽  
Olalekan O Oluwole ◽  
Aaron C Logan ◽  
Maria R. Baer ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Phase 1 ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

ZUMA-3 is a phase 1/2 study evaluating KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult relapsed/refractory (R/R) B-ALL. We report the phase 1 results. Following fludarabine/cyclophosphamide lymphodepletion, patients received a single infusion of KTE-X19 at 2, 1, or 0.5×106 cells/kg. The rate of dose-limiting toxicities (DLTs) within 28 days following KTE-X19 infusion was the primary endpoint. KTE-X19 was manufactured for 54 enrolled patients and administered to 45 (median age: 46 years [range, 18-77]). No DLTs occurred in the DLT-evaluable cohort. Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 31% and 38% of patients, respectively. To optimize the benefit-risk ratio, revised adverse event (AE) management for CRS and NE (earlier steroid use for NE and tocilizumab only for CRS) was evaluated at 1×106 cells/kg KTE-X19. In the 9 patients treated under revised AE management, 33% had grade 3 CRS and 11% had grade 3 NE, with no grade 4/5 NE. The overall complete remission rate correlated with CAR T-cell expansion and was 83% in patients treated with 1×106 cells/kg and 69% in all patients. Minimal residual disease was undetectable in all responding patients. At 22.1 months (range, 7.1-36.1) median follow-up, the median duration of remission was 17.6 months (95% CI, 5.8-17.6) in patients treated with 1×106 cells/kg and 14.5 months (95% CI, 5.8-18.1) in all patients. KTE-X19 treatment provided a high response rate and tolerable safety in adults with R/R B-ALL. Phase 2 is ongoing at 1×106 cells/kg with revised AE management.

scholarly journals The emotion-valuation constellation: multiple emotions are governed by a common grammar of social valuation

2019 ◽  
Author(s):  
Daniel Sznycer ◽  
Aaron Lukaszewski
Keyword(s):  
United States ◽  
Cultural Differences ◽  
The United States ◽  
Cross Cultural ◽  
Social Value ◽  
Social Emotions ◽  
The Social ◽  
Social Valuation ◽  
Common Architecture ◽  
Substantial Degree

Social emotions are hypothesized to be adaptations designed by selection to solve adaptiveproblems pertaining to social valuation—the disposition to attend to, associate with, and aid atarget individual based on her probable contributions to the fitness of the valuer. To steerbetween effectiveness and economy, social emotions need to activate in precise proportion to the local evaluations of the various acts and characteristics that dictate the social value of self and others. Supporting this hypothesis, experiments conducted in the United States and India indicate that five different social emotions all track a common set of valuations. The extent to which people value each of 25 positive characteristics in others predicts the intensities of: pride (if you had those characteristics), anger (if someone failed to acknowledge that you have thosecharacteristics), gratitude (if someone convinced others that you have those characteristics), guilt (if you harmed someone who has those characteristics), and sadness (if someone died who had those characteristics). The five emotions track local valuations (mean r = +.72) and even foreign valuations (mean r = +.70). In addition, cultural differences in emotion are patterned: They follow cultural differences in valuation. These findings suggest that multiple social emotions are governed (in part) by a common architecture of social valuation, that the valuation architecture operates with a substantial degree of universality in its content, and that a unified theoretical framework may explain cross-cultural invariances and cultural differences in emotion.

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