Venetoclax Alone or in Combination With Chemotherapy in Paediatric and Adolescent/Young Adult Patients With Relapsed/Refractory Acute Myeloid Leukaemia
Bibliographic record
Abstract
BACKGROUND: Venetoclax is a potent, oral BCL-2 inhibitor approved as combination therapy for the treatment of adults with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. This study evaluated the safety and preliminary efficacy of venetoclax alone or combined with chemotherapy in paediatric and adolescent/young adult patients with relapsed/refractory AML. PROCEDURE: In this phase 1, open-label, two-part, multicentre study, paediatric and adolescent/young adult patients (<25 years of age) with relapsed/refractory AML were treated with venetoclax alone or in combination with hypomethylating agents or cytarabine. The study is registered with ClinicalTrials.gov, NCT03236857. RESULTS: A total of 37 patients received treatment with either venetoclax as a monotherapy (n = 3) or in combination with decitabine (n = 5), azacitidine (n = 19), low-dose cytarabine (n = 1) or high-dose cytarabine (HDAC; n = 9). Febrile neutropenia (57%), hypokalaemia (38%), and thrombocytopenia (35% [thrombocytopenia, 19%; platelet count decreased, 16%]) were the most common grade 3/4 treatment-emergent adverse events. Across all venetoclax combinations, the overall response rate (ORR) was 24% (9/37), and the median duration of response was 2.6 months (95% CI, 0.5-7.9). Among the combinations, ORR was 44% with venetoclax plus HDAC and 21% with venetoclax plus azacitidine. In biomarker-evaluable patients, responses to venetoclax plus chemotherapy were observed in patients harbouring mutations across a range of functional classifications and heterogeneous BH3 family member dependencies. CONCLUSIONS: Venetoclax alone or combined with chemotherapy was well tolerated in paediatric and adolescent/young adult patients with relapsed/refractory AML, with promising, although transient, responses with venetoclax plus HDAC or azacitidine.
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".