A 10-gene DNA sequencing panel could help identify which patients with myelodysplastic syndrome (MDS) are likely to relapse after allogeneic hematopoietic cell transplant (alloHCT), according to the results of a study published in JCO Precision Oncology.
The investigators performed targeted error-corrected DNA sequencing on blood samples from 48 patients from the randomized phase 3 Blood and Marrow Transplant Clinical Trials Network 0901 trial (NCT01339910) before patients were randomly assigned to receive either myeloablative conditioning (MAC; n=25) or reduced intensity conditioning (RIC; n=23) for alloHCT. The blood samples were analyzed for mutations within 10 gene regions that were previously found to be linked to worse clinical outcomes in RIC-receiving patients with AML: FLT3, IDH1, IDH2, JAK2, KIT, NPM1, NRAS, RUNX1, SF3B1, and TP53.
The gene panel identified mutations in 20 patients (42%). Data demonstrated that the presence of a detectable mutation was associated with poor outcomes. Specifically, patients with detectable mutations had a significantly higher 3-year relapse rate (40% vs 11%; P =0.022) and lower 3-year overall survival rate (55% v 79%; P =0.045) than those who did not have detectable mutations before RIC or MAC.
Among the patients with detectable mutations, those who received RIC were more likely to relapse than those treated with MAC. The 3-year relapse-free survival was 13% for the RIC group and 49% for the MAC group; this difference was found to be statistically significant (P =0.003).
The study authors concluded that the study provides evidence that targeted DNA sequencing in patients with MDS before transplant can identify those with the highest relapse rates after transplant. Though the choice of MAC rather than RIC “could dramatically lower the relapse rate” in patients with MDS and a detectable mutation present prior to conditioning, “this benefit was counterbalanced by increased transplant-related mortality,” they noted.
Nevertheless, the study “provides the rationale for clinical trials of personalized post-transplant maintenance for patients with MDS based on genetic assessment before transplant,” they concluded.
Dillon LW, Gui G, Logan BR, et al. Impact of conditioning intensity and genomics on relapse after allogeneic transplantation for patients with myelodysplastic syndrome. JCO Precis Oncol. Published online January 25, 2021. doi:10.1200/PO.20.00355