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Record W2961471425 · doi:10.1016/j.clml.2019.07.004

Long-Term Studies Assessing Outcomes of Ibrutinib Therapy in Patients With Del(11q) Chronic Lymphocytic Leukemia

2019· article· en· W2961471425 on OpenAlex
Thomas J. Kipps, Graeme Fraser, Steven Coutré, Jennifer R. Brown, Jacqueline C. Barrientos, Paul M. Barr, John C. Byrd, Susan O’Brien, Marie‐Sarah Dilhuydy, Peter Hillmen, Ulrich Jaeger, Carol Moreno, Paula Cramer, Stephan Stilgenbauer, Asher Chanan‐Khan, Michelle Mahler, Mariya Salman, Karl Eckert, Isabelle G. Solman, Sriram Balasubramanian, Mei Cheng, Anil Londhe, Joi Ninomoto, Angela Howes, Danelle F. James, Michael Hallek

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueClinical Lymphoma Myeloma & Leukemia · 2019
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsJuravinski Cancer CentreMcMaster University
FundersCilagJanssen PharmaceuticalsTG TherapeuticsH. Lundbeck A/SBeiGenePharmacyclicsGenentechSunesisAstellas PharmaExelixisSun PharmaRegeneron PharmaceuticalsF. Hoffmann-La RocheAbbVieJanssen BiotechTeva Pharmaceutical IndustriesGilead SciencesJanssen Research and DevelopmentMorphoSysPfizerBiogenCelgeneAstraZenecaAmgenAlexion PharmaceuticalsRocheGlaxoSmithKline
KeywordsIbrutinibMedicineChronic lymphocytic leukemiaOncologyInternal medicineLeukemia

Abstract

fetched live from OpenAlex

BACKGROUND: Certain genomic features, such as del(11q), expression of unmutated immunoglobulin heavy-chain variable region (IGHV) gene, or complex karyotype, predict poorer outcomes to chemotherapy in patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: We examined the pooled long-term follow-up data from PCYC-1115 (RESONATE-2), PCYC-1112 (RESONATE), and CLL3001 (HELIOS), comprising a total of 1238 subjects, to determine the prognostic significance of these markers in patients treated with ibrutinib. RESULTS: With a median follow-up of 47 months, ibrutinib-treated patients had longer progression-free survival (PFS) than patients treated in the comparator arm, regardless of genomic risk factors. Among patients treated with ibrutinib, we found that high-risk genomic features were not associated with shorter PFS (63-75% across all subgroups at 42 months) or overall survival (79-83% across all subgroups at 42 months). Surprisingly, we observed that ibrutinib-treated patients with del(11q) actually had a significantly longer PFS than ibrutinib-treated patients without del(11q) (42-month PFS rate 70% vs. 65%, P = .02). CONCLUSION: These analyses not only demonstrate that genomic risk factors previously associated with poor outcomes lose their adverse prognostic significance but also that del(11q) can be associated with a superior PFS with ibrutinib 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.

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)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.158
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.046
GPT teacher head0.379
Teacher spread0.333 · 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