S822 NIVOLUMAB AND BRENTUXIMAB VEDOTIN‐BASED, RESPONSE‐ADAPTED TREATMENT IN PRIMARY REFRACTORY AND IN PEDIATRIC PATIENTS WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA IN CHECKMATE 744
Bibliographic record
Abstract
Background: Current first salvage therapies (tx) for younger patients (pts) with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) are associated with variable cure rates and long‐term toxicities. New strategies are required, especially in primary refractory and pediatric pts. In adult R/R cHL, first salvage with nivolumab + brentuximab vedotin (BV) resulted in 82% objective response rate (ORR) with 61% complete metabolic response (CMR; Herrera et al. Blood 2018). CheckMate 744 (NCT02927769) is an ongoing phase 2 study evaluating a risk‐stratified, response‐adapted approach using nivolumab, BV, and bendamustine in children, adolescents, and young adults with R/R cHL. In the standard‐risk cohort, the regimen was well tolerated and resulted in high CMR rates prior to consolidation with high‐dose chemotherapy and autologous transplantation (auto‐HCT; Harker‐Murray et al. ASH 2018). Aims: To assess efficacy and safety of this risk‐stratified, response‐adapted approach in primary refractory pts, and in pediatric pts (aged <18 y) in CheckMate 744, with a focus on the nivolumab + BV induction phase. Methods: Pts aged 5–30 y, after 1 prior tx without auto‐HCT were eligible. Risk stratification to the standard‐risk cohort (R2) was based on disease stage at diagnosis, time to relapse, B symptoms or extranodal disease at relapse, extensive disease with radiation tx (RT) contraindicated at relapse, or relapse in a prior RT field. In the #R2 cohort, pts received 4 cycles of induction tx with nivolumab + BV. Tx could be administered in the outpatient setting at the investigator's discretion. Tumors were assessed after every 2 cycles by investigators and blinded independent central review (BICR) per Lugano 2014 criteria. Pts who achieved CMR proceeded to consolidation with high‐dose chemotherapy/auto‐HCT. Pts with suboptimal response after induction received 2–4 cycles of BV + bendamustine intensification and proceeded to consolidation if they achieved CMR. Primary endpoint was CMR rate per BICR any time before consolidation. Efficacy and safety in primary refractory pts, and in pts aged <18 y were post hoc analyses. Results: 44 pts were treated in the #R2 cohort. At baseline, median age was 16 y; 31 pts (70%) were aged <18 y and 24 pts (55%) had primary refractory disease. Median duration of follow‐up was 43 wk overall and 47 wk in pts aged <18 y. Ten pts aged <18 y entered intensification; of these, only 2 received 4 intensification cycles. BICR‐assessed CMR rates and ORR after induction and at any time prior to consolidation for primary refractory pts and pts aged <18 y are shown in the Table. Overall, 12/44 pts (27%) experienced a grade 3–4 tx‐related adverse event (TRAE). Among pts aged <18 y, 10/31 (32%) experienced a grade 3–4 TRAE, most commonly neutropenia (2/31; 6%). There were no deaths or TRAEs leading to discontinuation. Tx‐related immune‐mediated AEs were all grade 1‐2, and were maculopapular rash, hypersensitivity, and infusion‐related reaction (1 pt each). Summary/Conclusion: Response‐adapted tx with nivolumab + BV achieved high CMR rates in primary refractory pts with cHL after 4 cycles of induction. In pediatric pts with a standard risk of relapse, induction with nivolumab + BV, followed by BV + bendamustine intensification for suboptimal response, demonstrated high CMR rates and a favorable safety profile prior to consolidation. image
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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".