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Review
. 2022 May 14;14(10):2434.
doi: 10.3390/cancers14102434.

Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia?

Rory M Shallis  1 , Jan P Bewersdorf  2 , Maximilian F Stahl  3 , Stephanie Halene  1 , Amer M Zeidan  1
Affiliations
Review

Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia?

Rory M Shallis et al. Cancers (Basel). .

Abstract

The currently available therapeutic options for patients with TP53-mutated acute myeloid leukemia (AML) are insufficient, as they translate to a median overall of only 6-9 months, and less than 10% of patients undergoing the most aggressive treatments, such as intensive induction therapy and allogeneic hematopoietic stem cell transplantation, will be cured. The lack of clear differences in outcomes with different treatments precludes the designation of a standard of care. Recently, there has been growing attention on this critical area of need by way of better understanding the biology of TP53 alterations and the disparities in outcomes among patients in this molecular subgroup, reflected in the development and testing of agents with novel mechanisms of action. Promising preclinical and efficacy data exist for therapies that are directed at the p53 protein rendered dysfunctional via mutation or that inhibit the CD47/SIRPα axis or other immune checkpoints such as TIM-3. In this review, we discuss recently attractive and emerging therapeutic agents, their preclinical rationale and the available clinical data as a monotherapy or in combination with the currently accepted backbones in frontline and relapsed/refractory settings for patients with TP53-mutated AML.

Keywords: AML; TP53; acute myeloid leukemia; leukemia; p53.

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Conflict of interest statement

R.M.S. participated in Advisory Boards for Bristol Myers Squibb and Gilead Sciences, Inc. J.P.B. has no conflicts to disclose. M.F.S. consulted for Curis Oncology, Haymarket Media and Boston Consulting and participated in Advisory Boards for Novartis. S.H. consulted for Forma Therapeutics. A.Z. has consulted for AbbVie, Acceleron, Agios, Amgen, Aprea, Astellas, AstraZeneca, BeyondSpring, Boehringer Ingelheim, Cardiff Oncology, BMS, Daiichi Sankyo, Epizyme, Genentech, Gilead, Kura, Incyte, Ionis, Loxo Oncology, Janssen and Novartis; served on clinical trial committees for AbbVie, BioCryst, BMS, Geron, Gilead, Kura, Loxo Oncology and Novartis and received research funding from AbbVie, Acceleron, ADC Therapeutics, Amgen, Aprea, Astex, Boehringer Ingelheim, Cardiff Oncology, BMS, Incyte, Jasper, Jazz, Novartis and Pfizer. None of these relationships were related to this work.

Figures

Figure 1
Figure 1
Emerging frontline agents for the treatment of TP53-mutated acute myeloid leukemia.
See this image and copyright information in PMC

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