A Ruxolitinib Individual Supply Program for Patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
Bibliographic record
Abstract
Abstract Abstract 5170 Background: There are currently no approved, effective drug therapies for myelofibrosis (MF). Ruxolitinib (INC424), a potent and selective oral JAK1 and JAK2 inhibitor, has recently demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms, role functioning, and quality of life in 2 phase 3 studies in patients with MF. Both studies met their primary endpoint of the proportion of patients with ≥35% reduction in spleen volume at 24 weeks (COMFORT-I) and at 48 weeks (COMFORT-II): 41.9% vs 0.7% (ruxolitinib vs placebo, P <.0001) and 28.5% vs 0% (ruxolitinib vs best available therapy, P <.0001), respectively. The most common grade ≥3 hematologic adverse events (AEs) were thrombocytopenia and anemia, which were manageable and rarely led to discontinuation (COMFORT-I: n=1 each; COMFORT-II: thrombocytopenia, n=1; anemia, n=0). Because of the limited available treatment options and medical need, ruxolitinib has been made available through an individual supply program (ISP) outside the United States. Methods: Patients with PMF, PPV-MF or PET-MF who are determined by their physicians to be in need of treatment are considered for eligibility, irrespective of JAK2 mutation status. As in the COMFORT studies, the starting dose of ruxolitinib is determined on the basis of baseline platelet count and can be adjusted for efficacy and safety. Dose changes during treatment are registered, and AEs and serious AEs (SAEs) are monitored throughout the study. Results: To date, 231 patients have been screened at more than 150 study sites in 28 countries, including Canada, Australia, and locations in Europe, Latin America, the Middle East, and Asia. The baseline characteristics for patients whose requests for access were approved/enrolled (n=200) and denied/pending (n=31) are shown below (Table). The patient characteristics are generally similar to those expected in the overall MF patient population. To date, the proportion of patients with the JAK2V617F mutation enrolled in this ISP (68.5%) is higher than that for the general MF population (50–60%) and may reflect the tendency of physicians to include more JAK2V617F-positive patients in the ISP, even though ruxolitinib has demonstrated comparable efficacy in both patient types (Verstovsek S, et al. N Engl J Med. 2010;363(12):1117–1127). Thrombocytopenia and herpes zoster were each reported as an AE in 1 patient, and no SAEs have been reported. Conclusions: Ruxolitinib is currently the only drug to have completed phase 3 studies for the treatment of MF and has garnered a substantial number of requests for access through the individual supply program. Disclosures: Barosi: Novartis: Consultancy. Cervantes:Bristol-Myers-Squibb: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Panagiotidis:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Janssen: Research Funding; GSK: Honoraria. Perez:Novartis: Employment. Orlando-Harper:Novartis: Employment. Martin:Novartis Pharma AG: Employment. Willenbacher:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AESCA: Honoraria, Research Funding. Ojeda:Novartis: Consultancy. Gisslinger:Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau; Aop-Orphan: Speakers Bureau. Knoops:Novartis: Consultancy.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.010 | 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".