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Record W4401913715 · doi:10.1002/hem3.146

Long‐term immune changes in patients with relapsed/refractory chronic lymphocytic leukemia following treatment with venetoclax plus rituximab

2024· article· en· W4401913715 on OpenAlexaff
Arnon P. Kater, Barbara Eichhorst, Carolyn Owen, Ulrich Jaeger, Brenda Chyla, Marcus Lefebure, Rosemary Millen, Yanwen Jiang, Maria Thadani‐Mulero, Michelle Boyer, John F. Seymour

Bibliographic record

VenueHemaSphere · 2024
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsUniversity of Calgary
FundersGenentechF. Hoffmann-La RocheAbbVie
KeywordsRituximabHypogammaglobulinemiaMedicineInternal medicineChronic lymphocytic leukemiaCD20GastroenterologyVenetoclaxRefractory (planetary science)AntibodyImmune systemImmunologyBendamustineLeukemia

Abstract

fetched live from OpenAlex

Abstract Immune dysregulation is a hallmark of chronic lymphocytic leukemia (CLL). Anti‐CD20 antibodies (e.g., rituximab [R]) can be combined with venetoclax (Ven) to treat CLL. However, anti‐CD20 antibodies can increase hypogammaglobulinemia risk, while the effects of Ven on immune dysregulation are still uncertain. We report long‐term immune changes in VenR‐ and bendamustine‐R (BR)‐treated patients with relapsed/refractory CLL in the MURANO trial (NCT02005471). Patients were randomized to fixed‐duration VenR (2 years Ven; VenR for the first 6 months) or BR (6 months). Immune cell levels were evaluated at the end of combination treatment (EOCT), end of treatment (EOT; VenR arm only), and 12 and 24 months post‐EOCT. Overall, 130/194 VenR‐ and 134/195 BR‐treated patients completed treatment without progressive disease. In patients who completed VenR combination therapy, median immunoglobulin (Ig)G and IgM levels decreased from baseline to EOT ( p ≤ 0.01 and p ≤ 0.0001, respectively); by 24 months, post‐EOT IgG had returned to baseline level and IgM had increased from baseline ( p ≤ 0.001). Median IgA levels increased from baseline to 12 ( p ≤ 0.0001) and 24 months post‐EOT ( p ≤ 0.0001). In BR‐treated patients, changes in IgG, IgA, and IgM levels across the assessed time points were not significant, and by 24 months, post‐EOCT IgG, IgA, and IgM were above baseline levels. Grade ≥3 infection rates on treatment were low. Overall, immune recovery was observed with VenR and BR, with stabilization of Ig levels after treatment. Post‐treatment infection rates were generally low, making these very tolerable therapies for CLL.

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)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.634
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.265
Teacher spread0.253 · 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 designRandomized trial
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

Citations3
Published2024
Admission routes1
Has abstractyes

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