Preliminary results of a phase II study of brentuximab vedotin using a response adapted design for the first line treatment of patients with Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or co-morbidity (BREVITY)
Bibliographic record
Abstract
P002: Introduction. Results of standard treatment for older patients (pts) with classical Hodgkin lymphoma (cHL) are sub-optimal and alternative approaches are required. Brentuximab vedotin (BV) is a CD30 targeted antibody-drug conjugate which in the pivotal* phase 2 trial in relapsed/refractory cHL produced an objective response rate of 75%, complete remission rate of 34% and manageable toxicity. BREVITY is a study of efficacy/tolerability of BV in older, frail or comorbid pts with previously untreated cHL. Methods. This was a phase II, Simon 2-stage, single arm study requiring 30 evaluable pts. Primary outcome was complete metabolic response rate (CMR, Deauville Score 1-3) by centrally reviewed PET-CT after 4 cycles of BV. Secondary outcomes included PFS, OS, toxicity and comorbidity assessment (CIRS-G). Inclusion criteria were previously untreated cHL stage 2 (with B symptoms and/or mediastinal bulk) or stages 3/4 with cardiac/respiratory compromise (at any age) or an ECOG score 1-3 and considered unfit for standard chemotherapy (in pts ≥60 yrs). BV dose was 1.8 mg/kg every 3 weeks, reduced to 1.2 mg/kg for toxicity. Pts in CMR/PMR after 4 doses BV continued to a total of 16 cycles if CT and/or PET-CT every 4 cycles confirmed ongoing response. PFS/OS data is not mature. Results. 38 pts were recruited Feb 2014-Oct 2015 at 12 UK centres; demographics are shown in Table 1. Table 1. 35 pts were treated and evaluable for toxicity, 31 are evaluable for response. Median follow-up for alive pts is 11.6(range 0.9, 21.4) months. A median of 4 cycles were given per pt (range 1, 16). 28(12%) cycles in 14 pts were modified due to toxicity and 11 pts stopped treatment due to adverse events (AEs). 695 AEs were reported of which 601(86%) were grade 1/2. 26(74%) pts had at least 1 AE ≥grade 3, most commonly infection, myelosuppression or neuropathy. CMR rate at PET4 was 25.8%(95% CI 13.7, 43.2) and combined CMR/PMR rate was 83.7(95%CI: 67.4, 92.9). To date 21(67.7%) pts have progressed. Discussion. In this study BV monotherapy produced a high objective response rate although the CMR rate after 4 cycles did not meet the pre-specified 40% level. Toxicity was greater than in the pivotal* study where pts were younger/fitter and led to treatment termination in some pts. Nevertheless BV is effective in this older comorbid population. A follow-on study incorporating BV at lower dose in combination with other agents and growth factor support aimed at improving the CMR rate is in development.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| 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 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".