296 | LIMITED STAGE DIFFUSE LARGE B CELL LYMPHOMA IN THE MODERN ERA: REAL‐WORLD OUTCOMES IN AN INTERNATIONAL STUDY OF OVER ONE THOUSAND PATIENTS
Bibliographic record
Abstract
Z. Loh, H. Johns, A. Khurana, J. Paludo, R. Puckrin, D. Stephens, J. W. Friedberg, G. Hapgood, M. Bishton, M. Saleh, C. Fletcher, D. Villa, L. H. Sehn, A. Ravindra, U. Farooq, A. Danilov, S. Walker, K. Lewis, L. Churilov, C. Y. Cheah, and E. A. Hawkes equally contributing author. Introduction: Diffuse large B-cell lymphoma presents as limited stage disease (LSDLBCL) in 30% of patients (pts). LSDLBCL has distinct biology and outcomes, compared to advanced stage. We report clinical features, treatment and outcomes from a large, international LSDLBCL cohort. Methods: Our multicentre retrospective study enrolled adult pts from 4 countries from Jan 2013-July 2019, with PET-staged I-II DLBCL. Analysis was restricted to pts treated with curative intent RCHOP chemotherapy +/− radiotherapy (RT). Time to event variables were estimated using Kaplan-Meier methods. Multivariable Cox proportional hazards regression model was performed and adjusted for age, sex, ECOG, stage, LDH, extranodal disease, & bulk ≥ 7.5 cm. Results: 1058 pts were identified with a median follow up of 62 months (range 2–187). Characteristics were as follows; median age 63y (range 18–91), 55% male, 89% ECOG 0–1, Stage I 54%, B symptoms in 18%, elevated LDH 30%, bulk ≥ 7.5 cm 24%, extranodal involvement 53%. Stage modified IPI (smIPI) was: 0 in 18%, 1 in 38%, 2 in 30%, 3–4 in 14%. Overall response (ORR) was 96% (CR 91%). 5yr PFS & OS was 79% (95% CI: 77–82) and 85% (95% CI: 83–87) respectively. Median PFS and OS was 13.1yrs (12.4-NR) and 14.6yrs (12.9-NR). 11% had a progression event (median time to progression 14 m, range 1.4–125); 62% occurred at 0–2y, 22% at 3–5y, & 16% at 5–10y. 179 pts died; 67 due to lymphoma, 26 due to infections and 24 due to other cancers. On multivariable analysis, age > 60 (HR2.9, 95% CI: 1.7–4.8), ECOG > 2 (HR2.4 (1.4–4.2)) and stage II disease (HR1.9 (1.2–2.9)) were significantly associated with inferior OS. The presence of extranodal disease was significantly associated with inferior PFS (HR1.5 (1.1–2.1)), along with age > 60 (HR1.5 (1.0–2.2)), ECOG > 2 (HR2.0 (1.2–3.2)) and stage II disease (HR1.8 (1.3–2.7)). 5y PFS for smIPI score 0–1, 2 and 3–4 was 84% (95% CI: 81–87), 80% (74–84) & 63% (54–71) respectively. PFS and OS were similar with RCHOPx4, RCHOPx3-4+RT, RCHOPx6-8 and RCHOPx6-8+RT (PFS p = 0.462; OS p = 0.380) (Figure 1). In pts aged 18–60, with ECOG 0–1, normal LDH and bulk < 7.5 cm (n = 194), 5y PFS and OS was 89% (83–93) and 95% (90–98); similar to the 5y PFS and OS of 94% (91–97) and 97%–98% (94–100) in the German FLYER trial (Poeschel Lancet 2019). Conclusion: LSDLBCL outcomes in our large cohort are similar between standard treatment groups, and to that of recent landmark clinical trials. A persistent pattern of relapse was observed, contrasting with the typical outcomes seen in advanced-stage DLBCL. Future research efforts should aim to refine risk stratification to improve prognostic accuracy and optimize adaptive management approaches. Keywords: Non-Hodgkin; Aggressive B-cell non-Hodgkin lymphoma Potential sources of conflict of interest: J. Paludo Honoraria: AbbVie (to institution) Other remuneration: Research funding (to institution): Karyopharm, Biofourmis, AstraZeneca R. Puckrin Honoraria: Abbvie, Astrazeneca, Beigene, Eli Lilly, Seagen, Incyte, Kite, Janssen, Roche M. Bishton Consultant or advisory role: Incyte, Roche, Lilly, AbbVie Honoraria: Roche, Takeda, Celltrion, Kite/Gilead, Lilly, Abbvie, Recordati Other remuneration: Research funding Roche and Takeda U. Farooq Consultant or advisory role: Kite, Morphosys E. A. Hawkes Consultant or advisory role: Roche*, Merck Sharpe & Dohme*, Astra Zeneca*, Gilead, Antengene, Novartis, Regeneron, Janssen, Specialised Therapeutics, Sobi . Educational grants: Astra Zeneca Other remuneration: Research funding (paid to institution): Roche, Bristol Myers Squibb, Merck KgA, Astra Zeneca, TG therapeutics and Merck A. Barraclough Honoraria: Gilead, Roche, Novartis, Beigene Educational grants: AstraZeneca
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".