ROBUST: PHASE III RANDOMIZED STUDY OF LENALIDOMIDE/R‐CHOP VS PLACEBO/R‐CHOP IN UNTREATED ABC‐TYPE DIFFUSE LARGE B‐CELL LYMPHOMA AND FEASIBILITY OF CELL OF ORIGIN SUBTYPING
Bibliographic record
Abstract
Introduction: The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is associated with inferior survival following chemoimmunotherapy. Lenalidomide, an immunomodulatory agent, has significant single-agent activity in relapsed/refractory DLBCL, predominantly ABC type, alone and in first line DLBCL plus R-CHOP (i.e., R2-CHOP). Until recently, real-time identification of cell of origin (COO) subtype as a biomarker to inform treatment decisions was not feasible due to technological limitations. The DLC-002 (ROBUST) randomized, phase III study (NCT02285062) is currently evaluating first line R2-CHOP vs placebo–R-CHOP in ABC-DLBCL, as determined by gene expression profiling (GEP). Methods: Patients are randomized 1:1 to oral lenalidomide (15 mg, d1-14/21) + standard R-CHOP or placebo–R-CHOP for 6 cycles with 2 optional, additional rituximab doses. Adult patients must have untreated, ABC-type CD20+ DLBCL, IPI score ≥ 2, and stage II–IV disease. The primary endpoint is progression-free survival (PFS). A central pathology lab determines COO type on FFPE biopsy samples within approximately 3 days using real-time GEP with the NanoString nCounter Dx analysis system. Subtype turnaround time is defined as number of days between central pathology sample receipt and when results are provided to the study site. Results: As of 24 Feb 2017, DLBCL subtyping was attempted in 1,530 patients, of whom 1,402 had samples successfully tested. COO results were 43% ABC and 57% non-ABC (GCB + unclassified). Samples from 128 patients, or about 8% of those screened for COO, were unacceptable due to various technical reasons such as incorrect or insufficient material, and low tissue RNA concentration or purity. Samples were analyzed in four central pathology labs located in the UK (X2), USA, and China, which together achieved a mean turnaround time of 2.56 days. As of 24 Feb 2017, 439 patients were randomized to treatment in ROBUST. Conclusions: Enrollment began in Jan 2015, with the goal of randomizing 560 patients by Aug 2017. Real-time COO assessment is feasible in this study with a short turnaround time. The percentage of ABC patients is similar to that reported in the literature. The ROBUST study is the first phase III trial of ABC-type DLBCL to use real-time GEP for patient eligibility, thus providing a significant advance in precision therapy in DLBCL. Keywords: activated B-cell-like (ABC); diffuse large B-cell lymphoma (DLBCL); lenalidomide.
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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 | 0.005 | 0.004 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
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".