Phase I/II Study of CYT387, a JAK1/JAK2 Inhibitor for the Treatment of Myelofibrosis
Gene Expression Profiling within the Context of JAK Inhibitor Therapy for Myelofibrosis: Correlation with Treatment Effect and Anemia Response
all I could find is this....from the Ash 2012 Annual meeting Emgargo Policy
"For oral presentations: the embargo time is the start time of the session in which the presentation is being made, or the beginning of the ASH press briefing containing the research, whichever comes first."
incy will present more data on their jakafi drug....this could get real interesting. "performance is difficult to rate, unless one has something to compare it to" . may take a little time to quantify all the data from 12/2011 to 12/2012 concerning cyt387 vs old to new incy data.JMHO
I may be mistaken but the Gene Expression Profiling is an oral poster session today after 5:30??
I would guess Dr. Pardanani will mention these facts in his Sunday presentation. Clearly...something is different in the structure of cyt387 compared to others and it is interesting that they, (ymi and mayo), are way ahead.....further than we all thought in discovering the differences....
1751 Gene Expression Profiling within the Context of JAK Inhibitor Therapy for Myelofibrosis: Correlation with Treatment Effect and Anemia Response
Program: Oral and Poster Abstracts
Session: 635. Myeloproliferative Syndromes - Basic Science: Poster I
Saturday, December 8, 2012, 5:30 PM-7:30 PM
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)
Animesh Pardanani, MBBS, PhD1, Rebecca R. Laborde, PhD1*, Terra L Lasho, MT, (ASCP)1*, Christy Finke, BS1*, Alexey A. Leontovich, PhD2* and Ayalew Tefferi, MD1
1Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
2Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN
Background: JAK inhibitors have significant palliative benefit in myelofibrosis (MF), mainly in the form of improved constitutional symptoms and reduced splenomegaly. Preliminary data suggests that CYT387, a JAK-1/2 inhibitor, also has the ability to produce anemia responses (ASH Annual Meeting, 2011). In general, the mechanism(s) underlying treatment effects of JAK inhibitors remain unclear but likely represent a drug-specific balance between anti-clonal activity and modulation of immuno cellular-cytokine pathways. We conducted a gene expression profiling (GEP) study using primary cells from MF patients undergoing therapy with CYT387 followed by correlation with clinical data.
Methods: Study subjects were enrolled in the Phase-1/2 study of CYT387 treatment in patients with primary (PMF), post-polycythemia vera (PPMF) or post-essential thrombocythemia (PTMF) myelofibrosis. Paired research samples were collected; the time points were pre-study and 12 weeks after commencing study treatment. PBMCs were purified from whole blood by Ficoll separation; RNA was isolated from this cell fraction for GEP analysis. Gene expression profiles were generated using Illumnia Human HT-12 v4 microarray. Pair wise analysis was conducted using the Wilcoxon signed-rank test with a p-value cutoff of 0.05 to generate lists of differentially expressed genes between assigned groups. Pathway analysis was conducted to identify relevant pathways enriched for differentially expressed genes. Comprehensive plasma cytokine profiling was performed using Multiplex Bead-Based Luminex technology (Invitrogen, Carlsbad, CA).
Results: Seventeen patients were studied based on sample availability; 11 (65%) mere male with median age of 66 years (range 53-85). Twelve (71%) were JAK2V617F mutation positive and the DIPSS-plus risk categorization was 10 (59%) high and 7 (41%) intermediate-2. All patients were evaluable for anemia response; 14 (82%) were red cell transfusion dependent at study start. Nine (53%) patients achieved anemia response by IWG-MRT criteria; of these, 8 patients achieved transfusion independence (minimum non-transfused hemoglobin level of 8 g/dL maintained for at least 12 weeks) and 1 had a sustained 2 g/dL increase in hemoglobin level above baseline.
The initial pair wise analysis to identify differential patterns of gene expression compared pre- and post-treatment groups (Figure 1A). This revealed a cluster of significantly (p