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
Bibliographic record
Abstract
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.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".