PF427 FOSTAMATINIB, A SPLEEN TYROSINE KINASE INHIBITOR, FOR THE TREATMENT OF WARM ANTIBODY AUTOIMMUNE HEMOLYTIC ANEMIA: INITIAL RESULTS OF THE OPEN‐LABEL EXTENSION PERIOD OF THE SOAR PHASE 2 STUDY
Bibliographic record
Abstract
Background: Warm antibody autoimmune hemolytic anemia (wAIHA) is a rare and often serious disease resulting from antibody‐mediated destruction of red blood cells (RBCs). The SYK inhibitor, fostamatinib, markedly improved Hgb levels in patients with wAIHA during a phase 2, open‐label, multicenter study, in which 9 of 21 (43%) met the primary endpoint (Hgb >10 g/dL with an increase of ≥2 g/dL from baseline by Week 24 without rescue therapy or RBC transfusion). Aims: We report the results of the ongoing extension period of the study. Methods: Adults with primary or secondary wAIHA had to have failed ≥1 prior treatment for wAIHA, have hemoglobin (Hgb) <10 g/dL, an IgG‐positive direct antiglobulin test, haptoglobin <10 mg/dL, and lactate dehydrogenase (LDH) >ULN. Fostamatinib 150 mg BID was taken orally with no food restriction (dose reduction permitted based on tolerability). To enter the extension, patients had to meet the primary endpoint OR show a marked improvement in Hgb and had to have tolerated study drug. Results: Nine patients who completed the initial treatment phase entered the extension: 7 patients met the primary endpoint, 1 was a late responder, and 1 had a beneficial trend during the initial treatment phase. For baseline characteristics, see table. Median Hgb levels increased over the study. Five of 9 patients have an ongoing response to fostamatinib as of July 2018, and none have had rescue therapy or an RBC transfusion. Six of 9 patients are still on the study, and 3 discontinued due to lack of response plus AE (1), consent withdrawn (1), and unknown (1). Nine patients had ≥1 AE, 6 with treatment‐related AEs. AEs were mostly mild to moderate, and the most common AEs were diarrhea and upper respiratory tract infection. Three Grade 3 AEs were reported in 2 patients. AEs resulted in dose reduction in 2 patients, dose interruption in 2, and study drug withdrawn in 1. Summary/Conclusion: Fostamatinib markedly improved Hgb levels in 9 of 21 (43%) patients with wAIHA during a phase 2, open‐label, multicenter study. Adverse events (AE) were manageable and consistent with those previously reported for fostamatinib in other conditions. A randomized, placebo‐controlled, Phase 3 trial is underway. image
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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 | 0.000 |
| 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".