Abstract
AbstractThe presence of measurable residual disease (MRD) prior to an allogeneic hematopoietic transplant (alloHCT) in Acute Myeloid Leukemia (AML) has been shown to be associated with an increased risk of post-transplant relapse. Since the Isocitrate Dehydrogenase genes (IDH1/2) are mutated in a considerable proportion of patients with AML, we studied if these mutations would serve as useful targets for MRD. Fifty-fiveIDH-mutated AML patients undergoing non-myeloablative alloHCT with post-transplant cyclophosphamide at a single center were sequenced at baseline using a multi-gene panel followed by targeted testing for persistentIDHmutations at the pre- and post-alloHCT timepoints by digital droplet PCR or error-corrected next generation sequencing. The cohort included patients who had been treated withIDHinhibitors pre- and post-transplant (20% and 17% forIDH1and 38% and 28% forIDH2). Overall, 55% of patients analyzed had detectableIDHmutations during complete remission prior to alloHCT. However, there were no statistically significant differences in overall survival (OS), relapse-free survival (RFS), and cumulative incidence of relapse (CIR) at 3 years between patients who tested positive or negative for a persistentIDHmutation during remission (OS:IDH1p=1,IDH2p=0.87; RFS:IDH1p=0.71,IDH2p= 0.78; CIR:IDH1p=0.92,IDH2p=0.97). There was also no difference in the prevalence of persistentIDHmutation between patients who did and did not receive anIDHinhibitor (p=0.59). Mutational profiling of available relapse samples showed that 8 out of 9 patients still exhibited the originalIDHmutation, indicating that theIDHmutations remained stable through the course of the disease. This study demonstrates that persistentIDHmutations during remission is not associated with inferior clinical outcomes after alloHCT in patients with AML.
Publisher
Cold Spring Harbor Laboratory