Circulating tumor DNA (ctDNA) status and clinical outcomes in patients (pts) with previously untreated diffuse large B-cell lymphoma (DLBCL) in the POLARIX study.
Bibliographic record
Abstract
7523 Background: the POLARIX study, pts with previously untreated DLBCL were randomized to Pola-R-CHP or R-CHOP (NCT03274492; Tilly et al. 2022). We previously validated the prognostic value of ctDNA at baseline and after one cycle of therapy in POLARIX (Herrera et al. 2022); here, we evaluate the relationship between ctDNA clearance and PFS and OS. Methods: Pts were included if baseline and longitudinal ctDNA results were available. Plasma ctDNA was measured at baseline, Cycle (C) 5 Day (D) 1, and end of treatment (EOT), with the AVENIO NHL CAPP-Seq assay (Stokowski et al. 2022). ctDNA clearance was determined as previously described (Herrera et al. 2022). PFS and OS according to ctDNA status were reported as landmarked hazard ratios (HR) and 3-yr rates. HRs were adjusted for IPI score (>2), region, bulky disease (>7.5cm), age (>60 years), and cell of origin. Results: At baseline, 654 pts had ctDNA results; 494 (76%) and 519 (79%) pts were evaluable at C5D1 and EOT, respectively. Undetectable ctDNA (ctDNA−) was achieved by 57% (152/265) of Pola-R-CHP-treated pts and 59% (135/229) of R-CHOP-treated pts at C5D1 (p=0.79), and by 66% (172/262) of Pola-R-CHP-treated pts and 67% (172/257) of R-CHOP-treated pts at EOT (p=0.83). Achieving ctDNA− was prognostic for PFS and OS in each treatment arm at C5D1 and EOT (Table). Pts in the Pola-R-CHP arm who had complete response (CR) with PET-CT and ctDNA− at EOT had superior PFS and OS compared with pts with CR and detectable ctDNA (ctDNA+) at EOT (PFS HR 0.30, 95% confidence interval [CI]: 0.14–0.66; OS HR 0.20, 95% CI: 0.07–0.60). This was not observed with R-CHOP (PFS HR 0.74, 95% CI: 0.34–1.63; OS HR 1.11, 95% CI: 0.30–4.16). Among pts with CR and ctDNA− at EOT, pts treated with Pola-R-CHP had superior PFS vs R-CHOP (HR 0.41, 95% CI: 0.21–0.82); this was not observed with OS (HR 0.41, 95% CI: 0.14–1.18). There was no statistically significant difference in PFS between treatment arms in pts with CR and ctDNA+ at EOT (PFS HR 1.20, 95% CI: 0.49–2.83). Conclusions: Achieving ctDNA− at C5D1 and EOT was prognostic for longer survival. Although no difference was observed in the number of pts with ctDNA− at EOT between arms, pts achieving CR and ctDNA− at EOT had superior PFS in the Pola-R-CHP vs the R-CHOP arm, suggesting deeper molecular responses in pts treated with Pola-R-CHP beyond the detection sensitivity of the assay used in this analysis. Clinical trial information: NCT03274492 . [Table: see text]
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| 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".