What Are the Prospects for Treating TP53 Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia?

TP53 is a key tumor suppressor gene involved in fundamental biological processes of genomic stability and is recurrently mutated in a subgroup of myelodysplastic syndromes and acute myeloid leukemia. These patients have unique clinical and molecular features resulting in dismal outcomes despite standard cytotoxic chemotherapy, and long-term survival is seldom achieved with allogeneic stem cell transplant. Upfront use of hypomethylating agents with or without venetoclax has resulted in a favorable initial response over intensive cytotoxic chemotherapy, albeit responses are nondurable, and the median overall survival is typically less than 6 to 8 months. In this review, we examine the evidence of conventional treatments and focus on the emerging novel therapeutic options, including targeted molecular and immunotherapies for this challenging molecular subgroup. Together, there are still significant unmet needs to improve outcomes of patients with TP53 mutated myelodysplastic syndromes and acute myeloid leukemia, and enrollment in clinical trials should be highly favored whenever they are available.