A Phase 3 Randomized Study of Remestemcel-L versus Placebo Added to Second-Line Therapy in Patients with Steroid-Refractory Acute Graft-versus-Host Disease
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Bibliographic record
Abstract
Uncontrolled studies have suggested that bone marrow-derived mesenchymal stem cells (MSCs) may be effective against acute graft-versus-host disease (aGVHD). We conducted a multicenter, randomized study to assess the efficacy of using ex vivo cultured adult human MSC (remestemcel-L) in addition to second-line therapy to treat steroid-refractory aGVHD (NCT00366145). In total, 260 patients, 6 months to 70 years of age, were enrolled from August 2006 to May 2009 and were randomized 2:1 to receive 8 intravenous infusions of remestemcel-L or placebo, given over 4 weeks, in addition to second-line therapy according to institutional standards. Four additional infusions over 4 weeks were indicated for patients with incomplete response at day 28. Randomization was stratified by aGVHD grade. Efficacy and safety were assessed through 180 days of follow-up, with the primary endpoint being durable complete response (DCR), defined as complete resolution of aGVHD symptoms for any period of at least 28 days after beginning treatment. Remestemcel-L did not meet the primary endpoint of greater DCR in the intent-to-treat population (35% versus 30%; P = 0.42). In post hoc analyses, patients with liver involvement who received at least 1 infusion of remestemcel-L had a higher DCR, and higher overall complete or partial response rate (OR) than those who received placebo (29% versus 5%; P = .047). Among high-risk patients (aGVHD grades C and D), remestemcel-L demonstrated significantly higher OR at day 28 than placebo (58% versus 37%; P = 0.03). Furthermore, pediatric patients had a higher OR with MSCs compared with placebo (64% versus 23%; P = .05). Similar rates of adverse events were observed between treatment groups. Remestemcel-L was safe and well tolerated. Results of this study did not demonstrate superior DCR compared with placebo when added to standard of care. The favorable clinical responses seen in some patient subsets may warrant further investigation.
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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 it