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