SWOG S1826, a randomized study of nivolumab(N)-AVD versus brentuximab vedotin(BV)-AVD in advanced stage (AS) classic Hodgkin lymphoma (HL).
Bibliographic record
Abstract
LBA4 Background: The addition of BV to initial chemotherapy improves overall survival (OS) in adults and PFS in pediatric patients (pts) with AS HL. However, frontline BV adds toxicity, most pediatric pts receive radiation therapy (RT), and 7-20% of pts still develop relapsed/refractory (RR) HL. The PD-1 pathway is central to the pathogenesis of HL and PD-1 blockade is effective in RR HL. The adult and pediatric cooperative groups of the National Clinical Trials Network (NCTN) conducted the randomized, phase 3 S1826 trial to evaluate N-AVD vs BV-AVD in pts with newly diagnosed AS HL. Methods: Eligible pts were ≥12 years (y) with stage 3-4 HL. Pts were randomized 1:1 to either 6 cycles of N-AVD or BV-AVD. Recipients of BV-AVD were required to receive G-CSF neutropenia prophylaxis vs optional with N-AVD. Pre-specified pts could receive RT to residually metabolically active lesions on end of treatment PET. Pts were stratified by age, international prognostic score (IPS), and intent to use RT. Response and disease progression were assessed by investigators using 2014 Lugano Classification. The primary endpoint was PFS; secondary endpoints included OS, event-free survival, patient-reported outcomes (PROs), and safety. Results: 994 pts were enrolled from 7/9/19 to 10/5/22; 976 were eligible and randomized to N-AVD (n=489) or BV-AVD (n=487). Median age was 27y (range, 12-83y), 56% of pts were male, 76% were white, 12% were black, and 13% were Hispanic. 24% of pts were < 18y, 10% were > 60y, and 32% had IPS 4-7. So far, < 1% of pts received RT. At the planned 2nd interim analysis (50% of total PFS events) the SWOG Data and Safety Monitoring Committee recommended to report the primary results because the primary PFS endpoint crossed the protocol-specified conservative statistical boundary. 30 PFS events occurred after N-AVD vs 58 events after BV-AVD. With a median follow-up of 12.1 months, PFS was superior in the N-AVD arm [HR 0.48, 99% CI 0.27-0.87, one-sided p=0.0005); 1y PFS: N-AVD, 94%, BV-AVD, 86%. 11 deaths (7 due to adverse events, AE) were observed after BV-AVD compared to 4 after N-AVD (3 due to AE). The rate of grade (gr) ≥ 3 hematologic AE was 48.4% (45.1% gr ≥ 3 neutropenia) after N-AVD compared to 30.5% (23.9% gr ≥ 3 neutropenia) after BV-AVD. Rates (any gr) of febrile neutropenia (5.6% N vs 6.4% BV), pneumonitis (2.0% N vs 3.2% BV), ALT elevation (30.7% N vs 39.8% BV), and colitis (1% N vs 1.3% BV) were similar. Hypo/hyperthyroidism was more frequent after N-AVD (7%/3% N vs <1% BV) while peripheral neuropathy (any gr) was more common after BV-AVD (sensory: 28.1% N vs 54.2% BV; motor: 4% N vs 6.8% BV). Conclusions: N-AVD improved PFS vs BV-AVD in pts with AS HL. Few immune AEs were observed and < 1% of pts received RT. Longer follow-up is needed to assess OS and PROs. S1826, the largest HL study in NCTN history, is a key step towards harmonizing the pediatric and adult treatment of AS HL. Funding provided by: National Cancer Institute of the National Institutes of Health U10CA180888 and U10CA180819 and Bristol-Myers Squibb. Clinical trial information: NCT03907488 .
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".