NGS-Based Test Accurately Detects Post–Allo-HSCT Relapse in AML, MDS

The next-generation sequencing–based AlloHeme test demonstrated accuracy and sensitivity in predicting relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to new data from the prospective ACROBAT study (NCT04635384) presented at the 2025 Tandem Meetings of the American Society for Transplantation and Cellular Therapy and the Center for International Blood and Marrow Transplant Research.1,2

A 1-year interim analysis of the ACROBAT study found AlloHeme accurate and sensitive for monitoring relapse after allo-HSCT in AML and MDS. | Image credit: Елена Бутусова - stock.adobe.com

AlloHeme, which measures small changes in mixed chimerism to predict relapse following allo-HSCT, showed predictive value for relapse post allo-HSCT, with a clinically meaningful median lead time to relapse of 36 days in 26 patients who experienced increased microchimerism (iMC) before or at relapse.1 This time frame is clinically meaningful, according to the press release.

“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,” Monzr M. Al Malki, MD, associate professor and director, Unrelated Donor Bone Marrow Transplant Program, City of Hope National Medical Center, said in a 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.”

A total of 287 individuals—163 patients with AML, 66 patients with MDS, and 58 with acute lymphoblastic leukemia—underwent allo-HSCT and subsequent monitoring with AlloHeme and were included in the study.2 The interim data presented at the Tandem Meetings included the MDS/AML group of 235 patients.

The patient population spanned 11 test sites in the US, and patients underwent AlloHeme testing at 14 time points following allo-HSCT (at 4, 6, 8, 10, and 12 weeks; then at 4, 5, 6, 9, 12, 15, 18, 21, and 24 months). The median (IQR) follow-up at the time of the interim analysis was 14 (9.3-8.2) months. iMC was defined as an increase of 0.2% or more between time points, and complete chimerism (CC) was defined as donor chimerism of 99.8% or higher at 3 months following allo-HSCT.

In analyses at 3 and 6 months post HSCT, patients with iMC showed a higher relapse rate compared with those without iMC (P values = .016 and < .001, respectively), with a time-varying risk effect (TVEM) model demonstrating an HR of 35.2 for relapse (95% CI, 15.5-80.3; P < .001) using iMC as a time-varying variable and nonrelapse mortality as a competing risk for relapse. The sensitivity, specificity, and negative predictive value of iMC of at least 0.2% were 93%, 76%, and 98%, respectively. The 0.2% increase threshold also showed a positive predictive value of 47% for relapse prediction.

In patients whose iMC was detected prior to a relapse event (63% of relapses), the median lead time from iMC to relapse was 50 (27-77) days. Patients who never showed CD33 CC (n = 30) showed a cause-specific HR of 12.2 (95% CI, 4.1-35.7) for relapse vs patients who had achieved CC (n = 199). In the TVEM model, patients who achieved CC and later lost it (n = 60) had an HR of 27.5 (95% CI, 10.9-69.4) vs those who maintained CC status (n = 139).

Overall, the interim results suggest AlloHeme is accurate and sensitive in monitoring relapse, with a clinically meaningful lead time to relapse prediction in patients who have undergone allo-HSCT for AML or MDS.

“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,” Marica Grskovic, PhD, CareDx chief strategy officer, said in a statement.1 “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.”

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 by AlloHeme predicts early relapse in patients with AML/MDS—interim results from the acrobat multicenter study. Presented at: 2025 Tandem Meetings, Honolulu, Hawaii, February 12-15. Abstract 7.