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Record W4386623512 · doi:10.1111/bjh.19058

Final report of <scp>TKI</scp> discontinuation trial with dasatinib for the second attempt of treatment‐free remission after failing the first attempt with imatinib: Treatment‐free Remission Accomplished by Dasatinib (<scp>TRAD</scp>) study

2023· article· en· W4386623512 on OpenAlexafffund
María Agustina Perusini, Igor Novitzky‐Basso, Eshetu G. Atenafu, Donna L. Forrest, Isabelle Bence‐Bruckler, Lynn Savoie, Mary‐Margaret Keating, Lambert Busque, Robert Delage, Anargyros Xenocostas, Elena Liew, Pierre Laneuville, Kristjan Paulson, Tracy Stockley, Jeffrey H. Lipton, Brian Leber, Dennis Dong Hwan Kim

Bibliographic record

VenueBritish Journal of Haematology · 2023
Typearticle
Languageen
FieldMedicine
TopicChronic Myeloid Leukemia Treatments
Canadian institutionsMcMaster UniversityToronto General HospitalUniversity of AlbertaLondon Health Sciences CentreHôpital de l'Enfant-JésusUniversité de MontréalHôpital Maisonneuve-RosemontQueen Elizabeth II Health Sciences CentrePrincess Margaret Cancer CentreVancouver General HospitalUniversity of CalgaryBC Cancer AgencyAlberta Health ServicesMcGill University Health CentreUniversity of OttawaCancerCare ManitobaUniversity Health NetworkOttawa HospitalDalhousie UniversityWestern UniversityUniversity of TorontoUniversity of British Columbia
FundersBristol-Myers Squibb CanadaPrincess Margaret Cancer Foundation
KeywordsDasatinibDiscontinuationMedicineImatinibInternal medicineTyrosine-kinase inhibitorDrug holidayOncologyImmunologyMyeloid leukemiaHuman immunodeficiency virus (HIV)Cancer

Abstract

fetched live from OpenAlex

Multiple studies have reported a significant treatment-free remission (TFR) rate of 50%-60% in patients with chronic myeloid leukaemia (CML) who discontinue tyrosine kinase inhibitor (TKI) therapy. However, the remaining half of these patients still require re-initiation of TKI therapy for leukaemia control. It remains unclear if TKI drugs should be switched for re-therapy in patients who failed the first TFR (TFR1) attempt. Our study attempted to determine whether dasatinib therapy after TFR1 failure post-imatinib discontinuation could improve the likelihood of TFR2. Of 59 patients who lost molecular response after imatinib discontinuation for TFR1, 55 patients (93.2%) were treated with dasatinib, of whom 49 (89.1%) regained MR4.5 or deeper response, with a median time of 1.85 months to achieve MR4.5. Dasatinib was discontinued in 35 patients for TFR2 attempt, of whom 26 patients (74.28%) lost MMR and 6 (17.14%) MR4. Risk factor analysis for the TFR2 after dasatinib discontinuation suggested three significant factors: (1) doubling time of BCR::ABL1 transcript following TFR1 attempt, (2) rapid regaining of molecular response following dasatinib therapy and (3) undetectable BCR::ABL1 transcript prior to TFR2 attempt. The present study showed that dasatinib does not increase the TFR2 rate in general, but a selected group of patients could benefit from this approach.

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)0.001
metaresearch head score (Gemma)0.003
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 score0.434
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
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 head0.033
GPT teacher head0.299
Teacher spread0.265 · 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

Citations20
Published2023
Admission routes2
Has abstractyes

Explore more

Same venueBritish Journal of HaematologySame topicChronic Myeloid Leukemia TreatmentsFrench-language works237,207