Outcome of TP53-mutated CCUS and the risk of progression to myeloid neoplasms.

Abstract

7059 Background: TP53-mutated ( TP53mut) myeloid neoplasms (MN) are aggressive leukemia with poor survival. A subset of TP53mut MN is preceded by TP53mut CCUS that is conventionally considered to be high-risk premalignant condition, though evidence supporting the notion is lacking. We studied outcomes of TP53mut CCUS compared to TP53 wild-type ( TP53wt) CCUS. Methods: Mayo Clinic Molecular Hematology Database (N=7593) was queried to identify patients (pts) harboring pathogenic variant(s) in exons 4-11 of the TP53 gene with ≥2% variance allele frequency (VAF). CCUS was defined using the 5th edition of the WHO Classification for MN. Results: Of 457 pts with TP53mut, 29 (5.9%) had TP53mut CCUS. The median age at diagnosis was 67 years, 17 (59%) were female, and 20 (69%) had received cytotoxic therapies. One and ≥2 TP53mut were seen in 26 (89.6%) and 3 (10.3%) pts, respectively. Median TP53mut VAF was 9% (range 3-42), 3 had TP53mut VAF ≥20%, and 4 (14%) had non-MDS defining cytogenetic anomalies. Of 16 pts with available follow up evaluation (median interval 22 months, Table), 3 (10.3%) progressed to TP53mut MN at 5, 13, and 14 months from diagnosis. We next compared outcomes of TP53mut CCUS to TP53wt CCUS (n=138). The proportion of pts developing MN was not different between TP53wt and TP53mut CCUS (18.1 vs 10.3%, P= .42). Progression free survival of TP53mut CCUS was comparable to TP53wt CCUS at 1- (77 vs 83%), 2- (67 vs 67%), and 5-years (67 vs 59%, P=.9). Similarly, overall survival of TP53mut vs TP53wt CCUS at 1- (81 vs 89%), 2- (76 vs 76%), and 5-years (76 vs 67%) was comparable ( P= .94). Conclusions: In contrast to the prevalent notion, TP53mut was not associated with a higher risk of MN progression or mortality compared to TP53wt CCUS. Majority of TP53mut clones showed remarkable stability over years. [Table: see text]