CareDx’s AlloHeme Shows Accuracy in Detecting Relapse Following AlloHSCT in AML and MDS

CareDx’s AlloHeme, a next-generation sequencing (NGS)-based assay, has demonstrated the ability to detect early relapse following allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to interim data from the prospective ACROBAT study (NCT04635384).¹ The results were presented at the 2025 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Honolulu, Hawaii, February 12 to 15, 2025, by Monzr M. Al Malki, MD, an associate professor and the director of the Unrelated Donor Bone Marrow Transplant Program at City of Hope National Medical Center.²

AlloHeme utilizes detection of increased mixed chimerism (iMC) at a threshold of 0.2% or greater in the recipient’s chimerism between 2 consecutive readings to predict relapse. The analytical cohort for the study included 141 patients with AML and 55 patients with MDS.

An interim analysis was conducted at 12 months postHSCT in order to determine the estimated diagnostic performance of AlloHeme. It was found to have a sensitivity of 0.93, a specificity of 0.88, a positive predictive value (PPV) of 0.58, and a negative predictive value (NPV) of 0.99, resulting in an area under the curve (AUC) of 0.90. Furthermore, Al Malki reported that for the patients who were iMC-positive, 25 relapsed during the 12 months postHCT period and after the second CD33 measurement, and 18 did not relapse during the 12 months postHCT period. On the other hand, for patients who were iMC-negative, 2 relapsed during the 12 months postHCT period and after the second CD33 measurement, and 128 did not relapse during the 12 months postHCT period.

AlloHeme’s performance 12 months postHSCT was also compared to relapse detection using STR-level thresholds of 1% and 5%. For STR 1%, sensitivity was 0.56, specificity was 0.93, PPV was 0.60, NPV was 0.92, and the AUC was 0.74. For STR 5%, sensitivity was 0.26, specificity was 0.96, PPV was 0.54, NPV was 0.88, and the AUC was 0.61. Thus, AlloHeme was deemed superior to STR 1% and STR 5%.

Notably, in the 26 patients in which iMC occurred before or at relapse, the median time from the iMC to clinical relapse was 36 days (IQR 20, 70 days). As such, Al Malki indicated that this window of time may allow for intervention aimed at preventing relapse. Although, he noted that further studies would be needed to assess the ideal nature, potential feasibility, and effectiveness of such interventions.

“The interim results of the ACROBAT study build upon our growth strategy to expand into hematology oncology,” Marica Grskovic, PhD, CareDx’s chief strategy officer, said in a statement.¹ “With AlloHeme, we can detect relapse after allogeneic stem cell transplantation prior to conventional methods, giving clinicians the significant lead time they need to intervene sooner. We are very pleased with these results demonstrating the high sensitivity of the AlloHeme assay and its selection for an oral presentation at the Tandem Meetings given the significant impact it may have on patient outcomes through earlier detection of malignancy recurrence.”

Additionally, Al Malki stated that with nonrelapse mortality as competing risk, iMC versus no iMC for relapse showed a hazard ratio of 47.5. Overall, he concluded that based on the study’s interim results, AlloHeme has the ability to predict relapse with a high degree of accuracy and a significant lead time in postHSCT AML and MDS.

“We are extremely pleased with the results of the ACROBAT study which demonstrates that AlloHeme is highly accurate in predicting risk of relapse in patients who have undergone a hematopoietic cell transplant,” Al Malki added to the statement.¹ “This study gets us one step closer to having a highly reliable molecular biomarker that enables us to assess the status of the stem cell engraftment and predict risk of relapse.”

REFERENCES
1. CareDx announces presentation of data at 2025 tandem meetings demonstratingstrong performance of AlloHeme in early relapse detection for hematologic malignancies. News release. CareDx, Inc. February 13, 2025. Accessed February 13, 2025. https://investors.caredx.com/news/news-details/2025/CareDx-Announces-Presentation-of-Data-at-2025-Tandem-Meetings-Demonstrating-Strong-Performance-of-AlloHeme-in-Early-Relapse-Detection-for-Hematologic-Malignancies/default.aspx
2. Al Malki MM, Sobecks R, Cutler C, et al.CD33 Microchimerism assessment byAlloHeme predicts early relapse in patients with AML/MDS—interim results from the acrobat multicenter study. Presented at: 2025 Tandem Meetings, Honolulu, Hawaii, February 12 to 15. Oral presentation.