Acrobat: A Multicenter Prospective Study to Monitor Chimerism in Post Allogeneic Hemopoietic Cell Transplant Patients with AML, ALL, or MDS for Prediction of Engraftment and Relapse

BACKGROUND:

Allogeneic hematopoietic cell transplantation (HCT) remains the treatment of choice for leukemia patients, yet its success is limited at least in part by disease relapse, which can be as high as 50% or more at two years post-HCT. While engraftment post-HCT is routinely measured by semi-quantitative fluorescent PCR of short tandem repeats (STRs), its low sensitivity (1-5%) limits its usefulness as a routine relapse monitoring tool. We have developed an ultra-sensitive, accurate, and precise microchimerism monitoring solution, AlloHeme that can potentially improve allogeneic HCT patient surveillance for engraftment and relapse. NGS-based AlloHeme can accurately measure microchimerism (mC, defined as <1% recipient DNA) with a limit of detection down to 0.035%. We hypothesized that detection of microchimerism and precise measurement of increasing mixed chimerism (iMC) using a highly sensitive test can predict disease relapse in patients post allo-HCT.

OBJECTIVES:

To study the role of mC and iMC measured by AlloHeme on relapse detection in patients with acute leukemias and myelodysplastic syndrome, we designed a prospective multicenter clinical trial - ACROBAT (Assessment of Chimerism in Recipients of Allogeneic Bone Marrow / Hematopoietic Cell Transplantation using AlloHeme Test).

METHODS:

The ACROBAT study will enroll approximately 260 allo-HCT recipients with AML, ALL and MDS across about 10 centers in the US. All patients will undergo serial chimerism monitoring in the first two years post-HCT. All AlloHeme testing will be conducted at CareDx's CLIA-certified/CAP-accredited laboratory. Chimerism will be monitored in the whole blood as well as for its constituent CD3+, CD15+ and CD33+ cellular subtypes. Bone marrow (whole bone marrow and CD34+ sub-type) chimerism will also be evaluated at specific timepoints.

The study will determine the predictive value of mC and iMC for relapse detection and the lead time to relapse. Univariable and multivariable sub-distributional hazard regression models and joint models of longitudinal and time-to-event data will be used to determine the impact of mC and iMC measured at different time points on relapse post-HCT. A time-dependent ROC curve will be used to investigate the predictive ability of AlloHeme, MRD, and chimerism by STR for relapse detection.

CONCLUSIONS:

The ACROBAT study is a multicenter prospective clinical study designed to evaluate the role of increasing mixed chimerism and microchimerism for early relapse detection in patients who have undergone allo-HCT for AML, ALL or MDS.

Kothari:CareDx, Inc.: Current Employment, Current equity holder in publicly-traded company. Dwivedi:CareDx, Inc.: Current Employment, Current equity holder in publicly-traded company. Egidio:CareDx, Inc: Current Employment, Current equity holder in publicly-traded company. Fei:CareDx, Inc: Current Employment, Current equity holder in publicly-traded company. Bell:CareDx, Inc.: Current Employment, Current equity holder in publicly-traded company. Kongtim:CareDx, Inc.: Consultancy. Grskovic:CareDx, Inc.: Current Employment. Ciurea:CareDx, Inc.: Consultancy.