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Safety outcomes in patients with acute myeloid leukemia receiving gemtuzumab ozogamicin and proceeding to allogeneic hematopoietic stem cell transplantation.

2024· article· en· W4399519785 on OpenAlexaff
Partow Kebriaei, Vincent T. Ho, Miguel‐Angel Perales, Nelli Bejanyan, Manmeet Kaur, Mei-Jie Zhang, Paul G. D'Amico, Simon Purcell, Stephanie Dorman, Erik Vandendries, Kofi Asomaning, Wael Saber

Bibliographic record

VenueJournal of Clinical Oncology · 2024
Typearticle
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsPfizer (Canada)
FundersPfizer
KeywordsGemtuzumab ozogamicinMedicineMyeloid leukemiaStem cellHematopoietic stem cell transplantationTransplantationHematopoietic cellHaematopoiesisLeukemiaOncologyInternal medicineCD34CD33

Abstract

fetched live from OpenAlex

6516 Background: Gemtuzumab ozogamicin (GO) is a CD33-directed antibody-drug conjugate approved by the FDA in 2017 for the treatment of newly diagnosed and relapsed/refractory (R/R) CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients of 1 month and older and 2 years and older, respectively. Previous data have associated GO with adverse events (AEs) including hepatotoxicity and hepatic veno-occlusive disease (VOD). Patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) may be at greater risk of VOD with GO. This study aimed to characterize AEs after HSCT in adult patients with AML who were treated with GO. Methods: This non-interventional post-authorization safety study used de-identified healthcare data from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Data were collected from 01 September 2017. Safety outcomes post-HSCT were evaluated in adult patients with newly diagnosed or R/R AML who received GO prior to first HSCT. Data cutoff was 04 July 2023. Results: We present the interim data of 157 patients from 24 centers with a median follow-up of 12.9 months (range, 3.0-49.7). At the time of HSCT, 84 patients were in first complete remission (CR1), 48 patients were in second CR (CR2) and 25 patients were in third or greater CR, relapse or primary induction failure (CR3, n=5; Rel, n=12; PIF, n=8). Most patients (n=105; 67%) received GO as first line therapy. Median lines of therapy prior to HSCT were 2, 3.5 and 5 in CR1, CR2 and CR3/Rel/PIF groups, respectively. Median age was 52.5 y (range, 18.7-74.9); 53% male. Time from diagnosis to first GO dose was <3 months for most patients (n=120; 76%). Total cumulative GO dose was 1-3 mg/m2 in 25 (16%), 4-6 mg/m2 in 28 (18%), 7-9 mg/m2 in 45 (29%) and ≥10 mg/m2 in 14 (9%) patients. The most common HSCT donor type was unrelated (n=93; 59%), and 55% of patients received myeloablative conditioning regimens. Non-fatal VOD was reported in 7 (4%) patients. Median time from HSCT to VOD was 0.9 months (range, 0.4-2.2). No VOD-related deaths occurred. Outcome probabilities for 6-month transplant-related mortality (TRM) were 8% (95% CI, 4-13) and 5% (95% CI, 2-8) for 100-day VOD. Conclusions: The use of GO appears to be safe prior to HSCT in adults with AML. Rates for 100-day VOD and TRM were comparable to those previously reported for patients with AML who received HSCT with or without prior GO. Clinical trial information: B1767034.

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)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
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 head0.040
GPT teacher head0.386
Teacher spread0.346 · 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 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

Citations0
Published2024
Admission routes1
Has abstractyes

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