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PS1067 AXICABTAGENE CILOLEUCEL (AXI‐CEL) IN PATIENTS WITH RELAPSED/REFRACTORY LARGE B CELL LYMPHOMA: PRELIMINARY RESULTS OF EARLIER STEROID USE

2019· article· en· W2950731790 on OpenAlexaff
Max S. Topp, Tom van Meerten, Martin Wermke, P.J. Lugtenburg, M. Minnema, Ki-Hak Song, Catherine Thiéblemont, Yuzhang Jiang, Vicki Plaks, A. Kerber, Marie José Kersten

Bibliographic record

VenueHemaSphere · 2019
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsMedicineCytokine release syndromeInternal medicineAdverse effectRefractory (planetary science)CohortTocilizumabLymphomaGastroenterologyClinical endpointSurgeryOncologyChimeric antigen receptorCancerDiseaseRandomized controlled trialImmunotherapy

Abstract

fetched live from OpenAlex

Background: Axicabtagene ciloleucel (axi‐cel) is an autologous anti‐CD19 chimeric antigen receptor (CAR) T cell therapy approved in the European Union and United States for patients with relapsed/refractory large B cell lymphoma with ≥ 2 prior systemic therapies. In the 2‐year follow‐up of ZUMA‐1, the objective response rate was 83% with a complete response rate of 58%. Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 11% and 32% of patients, respectively; 26% of patients received steroids, and 43% received tocilizumab (Locke et al. Lancet Oncol . 2019). A safety expansion cohort was added to evaluate the effect of earlier steroid use on the rates of these adverse events (AEs). Aims: To assess the impact of early steroid use on outcomes in patients treated with axi‐cel. Methods: Eligible patients with relapsed/refractory large B cell lymphoma were leukapheresed and received conditioning chemotherapy followed by a target dose of 2 × 10 6 anti‐CD19 CAR T cells/kg. Patients in this cohort received early steroid intervention starting at Grade 1 NE and at Grade 1 CRS when no improvement was observed after 3 days of supportive care. The primary endpoint for this cohort was incidence and severity of CRS and NE. Results: As of September 14, 2018, 21 of 40 planned patients received axi‐cel with a minimum follow‐up of 1 month (median, 2.6 months). The median age was 63 years (range, 36 – 73), 67% were male, 81% had disease stage III‐IV, 76% were relapsed/refractory to ≥ second‐line therapy, and 10% had relapsed post‐autologous stem cell transplantation. Seventy‐six percent of patients received steroids and 81% received tocilizumab. Most patients (81%) had Grade ≥ 3 AEs, most commonly neutrophil count decreased (33%), anemia (29%), and pyrexia (24%). Grade ≥ 3 NE occurred in 10% of patients; the most common symptoms were somnolence (10%) and confusional state (10%). Grade 1 and 2 NE occurred in 38% and 5% of patients, respectively. No patient had Grade ≥ 3 CRS; 33% of patients had Grade 1 CRS and 67% had Grade 2. There were no deaths due to AEs; 1 patient died due to disease progression. The objective response rate per investigator assessment was 76% with 48% of patients achieving a complete response. Pharmacokinetic data will be presented. Summary/Conclusion: Early use of steroids may help in managing severe CRS and NE by potentially reducing their incidence in patients treated with CAR T cell therapy without affecting response rates. Optimizing AE management may help to further improve the benefit:risk profile of CAR T cell therapy.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.047
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.239
Teacher spread0.227 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2019
Admission routes1
Has abstractyes

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