C086 | CHARACTERIZATION OF TP53 MUTATED ACUTE MYELOID LEUKEMIA TREATED WITH CPX-351: SUBANALYSIS FROM A LARGE REAL WORLD ITALIAN STUDY

CPX-351 has been approved for the treatment of patients (pts) with Acute Myeloid Leukemia (AML) with myelodysplasia related changes (AML-MRC) or therapy-related (t-AML). TP53 mutations (TP53m) affect at least 20-35% of such AML subtypes and confer dismal prognosis. We previously conducted a retrospective real life study about 513 pts who received CPX-351 in 38 italian centers since January 2019 (Guolo F. and Todisco E., paper submitted to AJH) showing that overall survival (OS) wasn’t significally influenced by TP53m, unless if a complex karyotype (CK) was also present. We now present a detailed subanalysis focused on 51 (39 AML-MRC and 12 t-AML) over 335 evaluable pts (15%) for whom TP53m were detected by Sanger (n=5) or Next Generation Sequencing (n=28) analysis or both (n=18). Median age was 63 years (range 23-73). Twenty-nine pts (57%) had CK, 18 (35%) monosomic karyotype (mainly monosomy 17, n=6, and monosomy 7, n=8), 6 (12%) del(17p) and 4 (8%) other abnormalities involving 17p. Allocation of pts based on TP53m allelic status was done according to Grob et al., Blood 2022 (Fig. 1a). Twenty-four pts (47%) obtained complete remission (CR). In univariate analysis for CR, molecular and cytogenetic characteristics were considered: del(17p) was the only variable with significant negative influence (p .021). Overall, 15/51 (29%) pts underwent allogeneic stem cell transplantation (allo-SCT). After a median follow up of 23,67 months (m) (CI 95% 21,47-25,86), median OS (mOS) of the entire population (n=51) was 9,5 m. Del(17p) was again the only factor having a significant negative impact on survival (mOS 4,7 m vs 13,6, p.005) (Fig. 1b). We observed a negative trend for biallelic status (mOS 13 m vs 28 for monoallelic (p .399)) and CK (mOS 11,5 m vs 32,5 (p .053)). In a landmark analysis of pts alive and in 1st CR who underwent allo-SCT (n=8, 33% of those who achieved CR), mOS was not reached; 4 of these (50%) had biallelic TP53m but none had del(17p). Among the 6 pts with del(17p) none achieved CR nor was alive at the last follow up. Although this is a retrospective study in which the incidence of TP53m is likely consequently underestimated, our analysis confirms that CPX-351 is a viable therapeutic option as bridge to allo-SCT also in a difficult subset like TP53m AML; further analyses and a larger sample are needed to clarify whether we can better stratify those carryng biallelic TP53m by confirming del(17p) as the most detrimental prognostic factor.