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CD28 on T cells as a Biomarker Predicting Response to Lenalidomide (Revlimid) in Non-del(5q) MDS Patients

Technology Application

MDS is a stem cell malignancy that largely afflicts individuals >60 years of age and often progresses to acute myeloid leukemia (AML). According to combined Surveillance, Epidemiology and End Results and Medicare claims data, at least 40-50,000 MDS patients are diagnosed annually in the USA, and approximately 70% of these patients have non-del(5q) MDS.Lenalidomide is currently sold by Celgene for the treatment of transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a del(5q). Revlimid one-year treatment costs for MDS patients have been estimated to be $52,596, and the duration of Revlimid treatment may range from a couple of rounds to many more, depending on how the individual patient responds to the drug.Celgene is seeking to expand the approved indications of lenalidomide (marketed as Revlimid) to include the 35,000 non-del(5q) MDS patients and is in Phase 3 clinical trials. The CD28 biomarker could help physicians determine which patients are among the approximately 26% of non-del(5q) patients that respond to lenalidomide, and which patients are among the 74% that do not respond.Our test is minimally invasive where a peripheral blood sample could be used to distinguish a responder from a non-responder before Revlimid treatment based upon the average percentage of CD28 positive CD4 or CD8 T-cells.

Detailed Technology Description

This diagnostic was developed using peripheral T cells from responsive and unresponsive MDS patients comparing their CD28 surface expression levels. Peripheral blood mononuclear cells were isolated from the blood of patients, then the CD3+ T-cell population is further separated and then stimulated. Using flow cytometry-based technology, detection of CD28 surface expression on that cell population was then used to correlate with MDS patient response to treatment with Revlimid. Low surface expression of CD28 on the T-cells of the subject suggests that the subject will be unresponsive or have diminished responsiveness to Revlimid treatment. In a small pilot study of 11 patients, non-responders had a lower percentage of CD28+ CD8 T-cells (p=0.0242) and CD28+ CD4 T-cells (p=0.0061) prior to Revlimid treatment.

*Abstract

CD28 on T cells is a biomarker that could be used to identify the 26% of non-del(5q) Myelodysplastic Syndrome (MDS) patients that will respond to lenalidomide to treat their anemia. Approximately 70% of newly diagnosed MDS patients have a non-del(5q), and while MDS patients with a del(5q) are already approved to receive lenalidomide, MDS patients with a non-del(5q) are not. Celgene currently has a Phase 3 clinical trial ongoing to approve lenalidomide for MDS patients with a non-del(5q). With 40-50,000 MDS patients diagnosed annually in the USA alone, if lenalidomide is approved for non-del(5q) MDS patients, then 70% of the newly-diagnosed MDS patients might need to be tested to find the 26% that respond to lenalidomide

Country/Region

USA