MINIMAL RESIDUAL DISEASE AND OUTCOMES IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (FL) IN THE PHASE III GADOLIN TRIAL OF OBINUTUZUMAB AND BENDAMUSTINE VS BENDAMUSTINE
Bibliographic record
Abstract
Introduction: Minimal residual disease (MRD) response after first-line treatment of FL may predict outcome; however, data are limited in the relapsed/refractory (r/r) setting. We previously described MRD assessment in r/r FL in the randomised GADOLIN study (NCT01059630; Pott C, et al. ASH 2015). Here, we report updated results for MRD status for the full population. MRD kinetics post-induction with respect to treatment efficacy and prognosis are reported for the first time. Methods: Patients (pts) received obinutuzumab (G) + bendamustine (B) (90 mg/m2) followed by G maintenance, vs B (120 mg/m2) alone. MRD was analysed by t(14;18) real-time quantitative PCR (RQ-PCR) and/or allele-specific immune gene (IGH or IGK) RQ-PCR in pts with a clonal marker at diagnosis: at mid-induction (MI), end of induction (EOI) and 6-monthly intervals to 24 months post EOI/discontinuation. MRD status was negative (i.e. MRD response achieved) if RQ-PCR and subsequent nested PCR were negative. Results: Of 335 randomised pts with FL, a clonal marker was detected in 228/319 (71%) pts with baseline samples (baseline-evaluable population, BEP). Compared with the BEP, the population with a detectable marker was enriched for higher stage, worse FLIPI and bone marrow (BM) involvement. MI and EOI samples were analysed for 88 and 118 pts, respectively. MRD negativity in peripheral blood (PB) occurred early during induction and was more frequent with G + B: 41/52 (79%) pts were MRD negative at MI vs 17/36 (47%) in the B arm (p = 0.0029). At EOI, MRD responses further increased: 54/63 (86%) pts receiving G + B achieved MRD negativity in PB and/or BM vs 30/55 (55%) in the B arm (p = 0.0002) (Table). Pts with complete/partial response who were MRD negative at EOI had improved PFS and OS vs MRD-positive pts; hazard ratios (adjusted for treatment): PFS, 0.33 (95% CI 0.19–0.56, p < 0.0001), OS, 0.39 (95% CI 0.19–0.78, p = 0.008). Clinical outcome and MRD kinetics were highly impacted by post-induction treatment; MRD negativity was generally sustained with G maintenance, whereas MRD-negative pts in the B arm (no maintenance) converted back to MRD positivity and relapsed early (Figure). Conclusions: MRD status at EOI was a sensitive marker of treatment efficacy, demonstrating that adding G to B-based treatment significantly contributes to the speed and depth of response. MRD-negative pts after G + B appeared to benefit from G maintenance, which potentially preserved MRD negativity and helped to control lymphoma regrowth. Keywords: follicular lymphoma (FL); minimal residual disease (MRD); obinutuzumab.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".