PYRAMID and LYM2034: Targeted randomized phase II studies of bortezomib with or without immunochemotherapy in newly diagnosed nongerminal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL), including rapid prospective non-GCB subtype identification.
Bibliographic record
Abstract
TPS226 Background: The recognition of prognostically distinct subtypes of DLBCL by gene expression profiling has, until now, not led to improved outcomes. Conducting targeted studies in prospectively identified, molecularly distinct entities is challenging. PYRAMID and LYM2034 are prospectively identifying and enrolling non-GCB patients (pts). This subtype has inferior outcomes vs GCB following (R-)CHOP alone (Lenz, NEJM 2008; Fu, JCO 2008). The rationale for these studies is provided by data suggesting bortezomib shows benefit specifically in non-GCB DLBCL resulting from inhibition of the critical NF-κB survival pathway, which is activated in the non-GCB subtype. Bortezomib + dose-adjusted EPOCH showed superior response rates and survival in non-GCB vs GCB relapsed DLBCL (Dunleavy, Blood 2009), and in newly diagnosed DLBCL, bortezomib + R-CHOP showed similar outcomes in GCB and non-GCB pts (Ruan, JCO 2010). Methods: PYRAMID is enrolling pts at 55 centers in the US; LYM2034 is enrolling pts at 86 sites in Canada, Australia, and countries in Central and South America, Europe, and Asia. Pts aged ≥18 yrs with previously untreated non-GCB DLBCL (PYRAMID: all stages; LYM2034: stages II–IV), ECOG PS 0–2, and ≥1 measurable tumor mass are eligible. Non-GCB tumor subtyping for both studies is done at a single central laboratory via the Hans immunohistochemical assay (Hans, Blood 2004). Non-GCB pts are then randomized to receive six 3-week cycles of R-CHOP alone (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, all on day 1, plus prednisone 100 mg, days 1–5), or bortezomib 1.3 mg/m2 on days 1 and 4 plus R-CHOP (PYRAMID) or bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 plus R-CAP (R-CHOP minus vincristine; LYM2034). The primary endpoint is PFS at 2 yrs in PYRAMID and CR rate in LYM2034. To date in PYRAMID and LYM2034, respectively, 100 and 167 DLBCL pts have been screened, and 34 of the planned 190 and 62 of the planned 164 non-GCB pts have been randomized. PYRAMID (NCT00931918) and LYM2034 (NCT01040871) are registered with ClinicalTrials.gov.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 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".