Garcia-Manero Previews Potential Therapeutic Standards in TP53-Mutated MDS/AML

October 15, 2020

Partner | Cancer Centers

In our exclusive interview, Guillermo Garcia-Manero, MD, discusses the prevalence of TP53 mutations in myelodysplastic syndromes and acute myeloid leukemia, the prognosis these mutations confer, and the development of eprenetapopt and magrolimab in this patient population.

Welcome to a very special edition of OncLive On Air! I’m your host today, Caroline Seymour.

OncLive On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Guillermo Garcia-Manero, MD, chief of the Section of Myelodysplastic Syndromes, deputy chair of Translational Research, and professor within the Department of Leukemia and Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, to provide perspective on the current paradigm for patients TP53-mutated myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), as well as the anticipated introduction of novel agents to the armamentarium.

Combinations of novel agents and hypomethylating agents are expected to replace the current frontline standard of care for patients with TP53-mutated MDS and AML, explained Garcia-Manero. Furthest in development in this regard is eprenetapopt, or APR-246, which has shown promising activity when used in combination with azacitidine in patients with TP53-mutated MDS and AML.

Results from a phase 2 trial conducted by the Groupe Francophone des Myélodysplasies, which were presented during the 2020 EHA Congress, demonstrated that the combination elicited a 76% response rate, which included a 53% complete response (CR) and CR with incomplete hematologic recovery rate and an 11% marrow CR rate.

Results from another phase 2 trial (NCT03072043) of eprenetapopt plus azacitidine, which were presented during the 2019 ASH Annual Meeting, echoed similar efficacy signals in this patient population. Specifically, the combination demonstrated an 88% response rate and a 53% CR rate.

In January 2020, the FDA granted a breakthrough therapy designation to the combination for the treatment of patients with MDS who harbor a susceptible TP53 mutation. The combination is now under evaluation in a phase 3 trial (NCT03745716) in patients with TP53-mutated MDS. If the results are positive, the combination will become the new standard of care in this setting, according to Garcia-Manero.

Additionally, the CD47-directed monoclonal antibody magrolimab has also shown encouraging activity in combination with azacitidine in a phase 1b trial among patients with TP53-mutated MDS and AML. The combination has since been taken forward into the phase 3 ENHANCE trial for exploration in patients with MDS.

In our exclusive interview, Garcia-Manero discussed the prevalence of TP53 mutations in MDS and AML and the prognosis they confer and shed light on the development of these 2 compounds that are being evaluated in this patient population.

Note: This episode was sponsored by Aprea Therapeutics.


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