Addressing Challenges in TP53-Mutant Acute Myeloid Leukemia

Eunice S. Wang, MD, spoke with CancerNetwork^® at the 2024 European Hematology Association (EHA) Congress about ongoing challenges in the acute myeloid leukemia (AML) field, particularly those related to managing TP53-mutated disease.

According to Wang, chief of the Leukemia Service of the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York, targeting TP53-mutant AML with immunotherapy is still a challenge in the field following presentations on data related to treatments such as the anti-CD47 agent magrolimab. Data presented at the meeting showed that treatment regimens including magrolimab plus azacitidine did not meet the primary end points among patients with myelodysplastic syndrome in the phase 3 ENHANCE study (NCT04313881)¹ and among those with AML in the phase 3 ENHANCE-3 study (NCT05079230).²

Wang stated that future meetings may help address whether immunotherapies, bispecific agents, or CAR T-cell therapies can impact the AML treatment paradigm.

Transcript:

TP53 still remains a challenge [in AML]. We’ve been somewhat disappointed. We’ve been excited every year or so only to be disappointed. [Regarding] the data out there, I don’t see anything that’s particularly targeting TP53 mutations [in] patients. Immunotherapy also remains a challenge. We had thought that because most of our conventional chemotherapy agents don’t work that we would see some impact of immunotherapeutics in TP53-mutant AML. For example, the recent failure of magrolimab being presented at this EHA meeting with the results of the ENHANCE trials, which are a great database for the efficacy of an [azacitidine combination] but didn’t show any improvement in an [azacitidine combination] with magrolimab, particularly in patients with TP53-mutant disease. That still remains a challenge, and we’ll need to be looking forward to future meetings as to how that’s being addressed and whether immunotherapeutic agents, bispecifics, and CAR T-cell therapy have yet to influence our treatment paradigms as of now for this difficult-to-treat myeloid malignancy.

References

1. Sallman D, Garcia-Manero G, Daver N, et al. Magrolimab (Magro) + azacitidine (AZA) vs placebo (PBO) + AZA in patients (PTs) with untreated higher-risk (HR) myelodysplastic syndromes (MDS): phase 3 ENHANCE study final analysis. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S181.
2. Daver N, Vyas P, Huls G, et al. Magrolimab vs placebo in combination with venetoclax and azacitidine in previously untreated patients with acute myeloid leukemia who are ineligible for intensive chemotherapy: the ENHANCE-3 study. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S138.