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2017 ASTS–Veloxis Vanguard Prize Recipients

ASTS gratefully acknowledges Veloxis Pharmaceuticals for their sponsorship of the 2017 Vanguard Prizes.
Dr. Ali Zarrinpar

Ali Zarrinpar, MD, PhD
The Dumont-UCLA Transplant Center

Dr. Ali Zarrinpar - Vanguard Prize
Synopsis: Post-transplant immunosuppressive drugs such as tacrolimus have narrow and inconsistent therapeutic target ranges. Inter- and intra-individual variability in dosing requirements necessitates empirical physician-titrated drug administration that results in frequent deviation from target ranges and can result in rejection, infection, or other toxicities. Multiple studies point to the importance of aggressive dosing and monitoring to minimize the risk of acute rejection and drug toxicities. The large array of genetic, environmental, and physiological factors that affect drug dose response make generating a predictive model-based algorithm for drug dosing very difficult. Conventional approaches to transplant immunosuppression present important challenges to regulating drug levels in the blood as several drugs are often co-administered, making it very difficult to accurately determine how patients will respond to variations in their therapy. A robust procedure to achieve individualized responses to the co-administration of multiple post-transplant drugs has thus far not been able to respond adequately to inter- and intra-patient variability that results from genetic/pharmacokinetic and other individualized factors. We have developed a computational approach named Phenotypic Precision Medicine (PPM) to utilize empirical clinical data to construct patient-specific visual maps that represent each individual’s phenotypic response to drug treatment. These visual maps then would allow us to rapidly pinpoint dosing parameters for that individual. Importantly, because this process does not require any a priori knowledge of disease mechanism, it can efficiently personalize drug dosing despite frequent changes to treatment regimens following transplantation.

 

Babak Orandi

Babak J. Orandi, MD, MSc, PhD
University of California, San Francisco

Babak Orandi - Vanguard Prize
Synopsis: Approximately one-third of adult kidney transplant waiting list candidates have anti-HLA antibodies, making these sensitized patients hard to match to compatible donors. Those patients who have a willing but incompatible live donor can participate in kidney paired exchanges, but the chance of finding a compatible match is still limited. Alternatively, these patients can undergo desensitization and subsequent incompatible live donor kidney transplantation. A prior study from a high-volume center demonstrated a significant survival benefit for incompatible live donor kidney transplantation compared to remaining on the waiting list, though the generalizability of that single center study was unclear. Our manuscript in the New England Journal of Medicine (2016;375(3):288-9) that was recognized by this Vanguard Prize was the result of a 22-center collaborative cohort study to determine the generalizability of a survival benefit for incompatible live donor kidney transplantation. This multicenter study demonstrated a significant survival benefit for incompatible live donor kidney transplant recipients as compared to those patients who did not undergo transplantation or waited for a deceased donor kidney transplant.‚Äč