AML-191 A Single Institution Experience on Clinical Outcomes of TP-53 Mutant Acute Myeloid Leukemia (AML)

Abstract

TP53 (tumor suppressor gene, 'the guardian of the genome') regulates DNA repair and cell division. TP53 mutations are observed in up to 20% of AML patients. It carries an adverse prognosis and is associated with inferior outcomes. Analyze TP53 mutations impact in AML patients. We reviewed patients with TP53 mutated AML treated at our institution. All cases of TP53 mutated AML (9 patients, 6.9%) of 130 AML patients were included. Nine patients were identified with newly diagnosed TP53 mutated AML. Fit non-APL patients received induction chemotherapy (IC) with purine analogues, cytarabine-anthracycline. Unfit patients received intensity chemotherapy (LIC) with a hypomethylating agent and venetoclax or cladribine, low dose cytarabine (LDAC) and venetoclax. Complete response (CR) rate and overall survival (OS) were analyzed. Among 130 patients with AML, we identified with TP53 mutations. 5(55%) were women. Races included Whites (n=2), Blacks (n=5) and Hispanics (n=2). Median age was 66 years (range, 41-80). Eight patients (88%) had complex cytogenetics. A coexisting IDH1 and DNMT3A mutation were present in 2 and 1 patient, respectively. 2 patients received FIA, and none achieved a CR. One patient treated with FIA developed severe neutropenic typhlitis and multiorgan failure. Unfit patients received HMA alone (n=2), HMA+ Ven (n=3), Cladribine, LDAC and Ven (n=2). Among 3 patients treated with HMA plus Ven; 2 achieved a CR. 2 patients treated with cladribine, LDAC, and Ven achieved CR after first cycle, and both remain in CR at a mean follow-up of 5 months. None received allogenic stem cell transplant (ASCT) in CR 1, but one patient underwent ASCT in CR 2 and died 2 months after transplant from graft failure and infection. Median OS in the entire cohort was 180 days (95% CI. 39.0-393.0 days). Our analysis though small in numbers seems to confirm the poor response to intense cytotoxic chemotherapy in TP53 mutant AML as described in recent medical literature (Short et al., Blood Advances, 2022). LIC is well tolerated and can be used as an effective bridging strategy to ASCT.