First Analysis of the Completed Mabthera International (Mint) Trial in Young Patients with Low-Risk Diffuse Large B-Cell Lymphoma (DLBCL): Addition of Rituximab to a CHOP-Like Regimen Significantly Improves Outcome of All Patients with the Identification of a Very Favorable Subgroup with IPI=O and No Bulky Disease.
Bibliographic record
Abstract
Abstract Rituximab has been shown to improve outcome in elderly patients with DLBCL (Coiffier et al., NEJM, 2002), but there is only limited data for young low-risk patients. In an intergroup study conducted in 18 countries, untreated patients (18–60 years) with low-risk CD20+ DLBCL (IPI 0 or 1, stages II-IV and stage I with bulk) were randomized to receive 6 cycles of a CHOP-like regimen (CHEMO) or the same chemotherapy plus rituximab 375 mg/m2 given on days 1, 22, 43, 64, 85, and 106 (R-CHEMO). Radiotherapy was planned to sites of initial bulk and/or extranodal involvement. The primary endpoint was time to treatment failure (TTF). Between 05/2000 and 10/2003, 824 patients were recruited. A first planned interim analysis was performed on 326 evaluable patients in November 2003 and let the independent review committee recommend the early stopping of the MInT trial on Dec 5, 2003, with 59 patients still under chemotherapy (28 CHEMO; 31 R-CHEMO). These were censored for this analysis. We here present the first full-set analysis on 823 evaluable patients (410 CHEMO; 413 R-CHEMO) with data base status as of Aug 2nd, 2004. Patient characteristics were: median age 47 years; IPI=1: 57%; stages III/IV: 28%; elevated LDH: 29%; bulky disease: 49%. Toxicity was not different in the two arms. After a median time of observation of 22 months, R-CHEMO patients had a significantly longer TTF (p<0.00001), with estimated 2-year TTF rates of 60% (CHEMO) vs 76% (R-CHEMO). Complete remission (CR) rates of evaluable patients (CR) were significantly different (67% CHEMO vs 81% R-CHEMO, p<0.0001) as were the rates of progressive disease during treatment (15% vs 4% , p<0.00001). Similarly, overall survival was significantly different (p<0.001), with 2-year survival rates of 87% (CHEMO) and 94% (R-CHEMO), respectively. The rate of lymphoma-associated deaths was reduced by two thirds with R-CHEMO. Using a Cox proportional hazard model for the primary endpoint TTF, treatment arm (p<0.00001), bulky disease (p<0.0001) and IPI (p<0.001) were significantly associated with the risk of an event. The benefit of R-CHEMO was demonstrated for all patients irrespective of these risk factors. However, 2-year TTF after R-CHEMO in patients with bulky disease and/or IPI=1 was significantly worse (p<0.001) than in patients with IPI=0 and no bulk (71% vs 90%, respectively), proposing two novel subgroups of young low-risk patients with a favorable and less favorable outcome in the era of combined rituximab/CHOP-like chemotherapy. The combination of 6 cycles of a CHOP-like chemotherapy with rituximab sets the standard for young low-risk patients with CDD20+ DLBCL. While further improvement will be difficult to demonstrate for the favorable (IPI=0, no bulk) subgroup, it is still warranted with regard to TTF for the less favorable subgroup (IPI=1 and/or bulk).
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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 | 0.009 | 0.007 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.006 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".