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Record W2884362356 · doi:10.1038/s41375-018-0210-1

Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia

2018· article· en· W2884362356 on OpenAlexaff
Robert J. Kreitman, Claire Dearden, Pier Luigi Zinzani, Julio Delgado, Lionel Karlin, Tadeusz Robak, Douglas E. Gladstone, Philipp le Coutre, Sascha Dietrich, Mirjana Gotić, Loree Larratt, Fritz Offner, Gary J. Schiller, Ronan Swords, Larry Bacon, Monica Bocchia, Krimo Bouabdallah, Dimitri Breems, Agostino Cortelezzi, Shira Dinner, Michael Doubek, Bjørn Tore Gjertsen, Marco Gobbi, Andrzej Hellmann, Stéphane Leprêtre, Frédéric Maloisel, Farhad Ravandi, Philippe Rousselot, Mathias Rummel, Tanya Siddiqi, Tamar Tadmor, Xavier Troussard, Cecilia Arana Yi, Giuseppe Saglio, Gail J. Roboz, Kemal Balic, Nathan Standifer, Peng He, Shannon Marshall, Wyndham H. Wilson, Ira Pastan, Nai-Shun Yao, Francis J. Giles

Bibliographic record

VenueLeukemia · 2018
Typearticle
Languageen
FieldImmunology and Microbiology
TopicToxin Mechanisms and Immunotoxins
Canadian institutionsUniversity of Alberta
FundersNational Cancer InstituteNational Institutes of HealthServierAstex PharmaceuticalsAstellas PharmaGilead SciencesAblynxTeva Pharmaceutical IndustriesSanofiCelgeneBristol-Myers SquibbAstraZenecaAmgenPfizer
KeywordsMedicineInternal medicineTolerabilityGastroenterologyPeripheral edemaNauseaDiscontinuationAdverse effectRefractory (planetary science)Minimal residual diseaseProgressive diseaseLeukemiaSurgeryDisease

Abstract

fetched live from OpenAlex

This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.009
GPT teacher head0.218
Teacher spread0.209 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized 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

Citations247
Published2018
Admission routes1
Has abstractyes

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