AVELUMAB MONOTHERAPY FOLLOWED BY A PET ADAPTED CHEMOTHERAPY APPROACH IN THE FIRST LINE TREATMENT OF CLASSICAL HODGKIN LYMPHOMA: INITIAL RESULTS FROM THE AVENUE WINDOW STUDY
Bibliographic record
Abstract
Introduction: Inhibitors of programmed cell death receptor 1 (PD1) used with chemotherapy result in high response rates and durable remissions in the first line (1L) treatment of classical Hodgkin Lymphoma (cHL). Avelumab is an inhibitor of the immune checkpoint PDL1, which is highly expressed by Reed-Sternberg cells, and has demonstrated activity in relapsed/refractory cHL. The AVENuE window study assessed the efficacy and safety of avelumab prior to response adapted chemotherapy as 1L treatment in cHL. It is the first study to report on PDL1 inhibition in this setting. Financial support was provided as an investigator sponsored research grant from Pfizer Ltd. Methods: Adult patients (pts) with advanced cHL were enrolled in this phase 2 study. Pts received 2 cycles (4 doses) of avelumab then underwent a PET/CT followed by 2 cycles of ABVD and PET/CT (iPET). iPET neg (Deauville score 1–3) pts received further 4 × AVD and PET pos (DS 4–5), escalated BEACOPP. RATHL study results were used as a historical comparison. The primary endpoint was overall response rate (complete & partial metabolic response: CMR/PMR) after 2 cycles of avelumab with >40% deemed worthy of further study and <20% considered unacceptable (5% 1-sided alpha, 90% power required 47 pts). Response was assessed as per modified Lugano criteria. Results: 47 pts were eligible. Median age 30 y (range: 17–58); 64% male; 23%, 26% and 51% had high risk stage II, stage III and IV disease respectively; 60% had B symptoms; 40% had IPSS of >2. 44 pts completed 2 cycles of avelumab (2 stopped due to toxicity, 1 due to site concerns over progressive disease (PD); indeterminate response (IR) by modified Lugano). 89% of subsequent ABVD/AVD cycles were delivered without delay (compared with 89% in RATHL). Overall response to 2 cycles of avelumab was 44.7% (90% CI: 32.2–57.7); CMR 11%; PMR 34%. The remainder were IR. iPET after 2 cycles of ABVD was positive in 5 pts (10.6%) (95% CI 3.5–23.1) versus 16.3% in the RATHL study. Pts with IR to avelumab did not show a worse response to ABVD compared with responders (87.5% vs. 88.0%). 5 pts had eBEACOPP of whom 4 converted to PET neg subsequently. With a median follow up of 14 months (range 4–32) there is a 1y PFS of 100% but 2 PDs have been reported at 14 and 23 months. Grade 3+ adverse events at least possibly related to avelumab occurred in 9 pts (20%) including one each of colitis, pneumonitis, autoimmune hepatitis, renal tubular acidosis and 2 reports of tumour flare. The research was funded by: Pfizer Keywords: Hodgkin lymphoma, immunotherapy Conflicts of interests pertinent to the abstract E. A. Hawkes Research funding: Merck KgA
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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 | 0.001 |
| 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".