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P009: Improved Overall Survival with First-Line Brentuximab Vedotin plus Chemotherapy in Patients with Advanced Stage III/IV Classical Hodgkin Lymphoma: An Updated Analysis of ECHELON-1

2022· article· en· W4303983518 on OpenAlexaff
Martin Hutchings, Stephen M. Ansell, Joseph M. Connors, Won Seog Kim, Andrea Gallamini, Radhakrishnan Ramchandren, Jonathan W. Friedberg, Ranjana H. Advani, Andrew M. Evens, Piotr Smolewski, Kerry J. Savage, Nancy L. Bartlett, Hyeon‐Seok Eom, Jeremy S. Abramson, Cassie Dong, Frank Campana, Keenan Fenton, Markus Puhlmann, David J. Straus, John Radford

Bibliographic record

VenueHemaSphere · 2022
Typearticle
Languageen
FieldMedicine
TopicLymphoma Diagnosis and Treatment
Canadian institutionsSpinal Cord Injury BC
Fundersnot available
KeywordsBrentuximab vedotinDacarbazineABVDMedicineHazard ratioInternal medicineVinblastineOncologyPopulationProgression-free survivalVincristineLymphomaConfidence intervalSurgeryChemotherapyHodgkin lymphomaCyclophosphamide

Abstract

fetched live from OpenAlex

Figure 1: Overall Survival in the Intent-to-Treat Population. New first-line treatment strategies for classical Hodgkin lymphoma (cHL) have not improved overall survival (OS) compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Five-year data from ECHELON-1 (NCT01712490) supported long-term progression-free survival (PFS) with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) in patients (pts) with previously untreated stage III/IV cHL vs ABVD, with a manageable long-term safety profile. We report an OS analysis from ECHELON-1 after a median of 6 years of follow-up (data cutoff June 1, 2021). Randomized pts (1:1) received ≤6 cycles of A+AVD (n=664) or ABVD (n=670) on days 1 and 15, every 28 days. The key secondary end point was OS (event-driven, type-1 error controlled) in the intent-to-treat population. Analysis of OS in prespecified subgroups was exploratory and not adjusted for multiplicity. PFS per investigator was reported for long-term follow-up. Deaths during follow-up, including reported causes of death per investigator, were summarized. We observed 39 OS events in the A+AVD arm vs 64 with ABVD, favoring A+AVD (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.40–0.88; p=0.009; median follow-up 73 months; Figure). OS was examined in prespecified subgroups; in a multivariable analysis adjusting for baseline demographic and disease factors, OS benefit was preserved (HR 0.53; 95% CI 0.34–0.83). PFS favored A+AVD (HR 0.68; 95% CI 0.53–0.86), consistent with prior reports. Subsequent therapy use was less frequent with A+AVD vs ABVD (135 [20%] vs 157 [24%]) including fewer autologous (44 [7%] vs 59 [9%]) and allogeneic stem cell transplants (4 [<1%] vs 12 [2%]) while use of radiation was similar (55 [8%] vs 58 [9%]), suggesting that the OS benefit was not due to undertreatment of pts in the ABVD arm. Fewer second malignancies (23 vs 32) and fewer deaths related to cHL or treatment complications (32 vs 45) or to second malignancies (1 vs 11) were reported with A+AVD vs ABVD, respectively; treatment-related deaths were comparable (8 vs 7). While fertility was not formally assessed, a total of 191 pregnancies were reported among pts and their partners (A+AVD 113; ABVD 78). More pts had peripheral neuropathy with A+AVD (443 [67%]) vs ABVD (286 [43%]), but most improved or resolved at last follow-up (379 [86%] vs 249 [87%]). To conclude, A+AVD significantly reduced risk of death vs ABVD by 41%. The long-term safety profile was manageable, consistent with prior reports.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.071
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.008
GPT teacher head0.240
Teacher spread0.232 · 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 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
Published2022
Admission routes1
Has abstractyes

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