ASH 2022 | Impact of allelic state on OS in TP53-mutant AML and HR-MDS
Jan Philipp Bewersdorf, MD, Memorial Sloan Kettering Cancer Center, New York City, NY, discusses the results of a posthoc analysis of the FUSION-AML-001 trial (NCT02775903) which evaluated the prognostic impact of mono-allelic and bi-allelic TP53 mutations in patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (MDS). The study showed that the outcomes of patients with TP53 mutations were worse compared to patients who were TP53 wild-type. However, the study also reported that there was no difference in OS between mono-allelic and bi-allelic status. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.
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Transcript (edited for clarity)
This is also a subset analysis of the FUSION trial that I talked previously about, this is as a recap. This is the combination of the durvalumab, the anti PD-L1 inhibitor plus azacitidine, compared to azacitidine monotherapy in older, intensive chemotherapy ineligible patients with AML or higher-risk MDS.
What’s especially, in MDS, been recognized more recently is that TP53 mutations have generally an adverse prognostic implication, but that the prognostic impact varies by the specific subtype of TP53 mutational status...
This is also a subset analysis of the FUSION trial that I talked previously about, this is as a recap. This is the combination of the durvalumab, the anti PD-L1 inhibitor plus azacitidine, compared to azacitidine monotherapy in older, intensive chemotherapy ineligible patients with AML or higher-risk MDS.
What’s especially, in MDS, been recognized more recently is that TP53 mutations have generally an adverse prognostic implication, but that the prognostic impact varies by the specific subtype of TP53 mutational status. For example, there’s data that shows that biallelic TP53 mutations are what’s actually driving the adverse prognosis, while patients with a monoallelic mutation tend to have a more favorable prognosis. However, the data is somewhat conflicting, and that’s why we conducted this post-hoc analysis, trying to use the randomized design to also limit any potential confounding that’s otherwise seen in real-world analyses.
We then used two different methods to assess allelic status, and one has been recently proposed by the International Consensus Conference, or ICC, this year, and the other one was published by Grob et al this year in Blood. What we could then see is, yes, TP53 mutations confer an adverse prognostic, have an adverse prognosis compared to TP53 wild-type status. However, there was no difference really in terms of monoallelic versus biallelic status, neither in AML nor in MDS patients.
So this adds to the literature and I think there’s just more analysis that’s needed to really reconcile those different results from the various studies.
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