Analysis of Varicella Zoster Virus Reactivation among Bortezomib-Treated Patients in the APEX Study.
Bibliographic record
Abstract
Abstract BACKGROUND: Bortezomib (btz, VELCADE®), a selective and reversible proteasome inhibitor, is approved for the second-line treatment of multiple myeloma (MM). There is a tendency for reactivation of varicella zoster virus (VZV;herpes zoster) among patients (pts) receiving immunosuppressive agents for cancer. Rates of VZV reactivation during btz therapy in phase 2 studies were reported to be 11% in SUMMIT and 13% in CREST. To investigate whether btz increases the incidence of VZV reactivation, data were reviewed from the phase 3 APEX trial of btz vs high-dose dexamethasone (dex) in pts with relapsed MM following 1–3 prior therapies. METHODS: The APEX trial was described previously [Richardson et al. N Engl J Med2005;352:2487–98]. Use of prophylactic anti-virals and anti-bacterials was not mandated by this protocol. RESULTS: Baseline characteristics, including age, prior ASCT, β2-microglobulin, and disease stage, were comparable between the btz and dex arms. The incidence of VZV reactivation was significantly higher with btz vs dex (13% [42/331] vs 5% [15/332], respectively; p=0.0002). Most VZV reactivation events in both arms were grade 1/2. Notably, the incidence of grade 3/4 events was similar between the two arms (1.8% [6/331] vs 1.5% [5/332]), as was the rate for serious adverse events (1.5% [5/331] vs 0.9%, [3/332], respectively). The incidence of other opportunistic infections, including VZV, was comparable between the btz and dex arms; 23% vs 20%, respectively. There were no deaths due to VZV reactivation in either arm. Median time to onset of VZV reactivation tended to be shorter in the btz arm vs dex, though this was not statistically significant (31 vs 51 days; p=0.221). At first assessment post VZV reactivation event, median ALC was significantly lower in the btz vs dex arm (1050 vs 1750 cells/μL; p=0.028). However, immediately prior to the event, median ALC was similar between arms (1030 vs 1100 cells/μL; p=0.529). CONCLUSIONS: Btz was associated with a higher incidence of VZV reactivation events than dex. The reasons for this are unclear and require further study. Preliminary evidence from recent studies has shown that this adverse event of btz could be overcome with the use of prophylactic acyclovir [Mateos et al. Blood 2006; Epub ahead of print].
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".