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Eprenetapopt combined with azacitidine as maintenance therapy after hematopoietic cell transplantation (HCT) improved outcomes for patients with TP53-mutant acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), a small multicenter phase II study showed.

Among the 33 patients who received the combination, median relapse-free survival (RFS) was 12.5 months, with a 1-year RFS rate of 59.9%, while median OS was 20.6 months, with a 1-year OS rate of 78.8%, reported Asmita Mishra, MD, of the Moffitt Cancer Center and Research Institute in Tampa, Florida, during a presentation at the Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy and the Center for International Blood and Marrow Transplant Research.

These results marked a substantial improvement in efficacy compared with historical data in this setting, Mishra noted.

"Given these exciting and encouraging results, we believe pursuing additional maintenance paradigms targeting TP53 is warranted and needed," she said.

Median time to relapse was 15.2 months, with a 1-year cumulative incidence of relapse of 38.3%.

The regimen was well tolerated in what was a highly pretreated population, Mishra noted. The most common hematologic treatment-emergent adverse events (TEAEs) of any grade were platelet count decreases (49%), anemia (39%), white blood cell count decreases (39%), and neutrophil count decreases (27%). The most common non-hematologic TEAEs of any grade were nausea (61%), vomiting (46%), dizziness (39%), fatigue (36%), diarrhea (33%), and tremor (33%).

Overall, 13 patients (39%) experienced graft-versus-host disease (GVHD). There were six cases of acute GVHD, none of which were grade 3 or 4. The incidence of chronic GVHD occurred in 14 patients, with one patient developing severe chronic GVHD (manifesting in eosinophilia and hyperbilirubinemia and leading to treatment discontinuation).

Patients were ineligible for the study if they had known HIV, hepatitis B or C infection, cardiac abnormalities, or concomitant malignancies, or if they had received prior azacitidine, decitabine, or an investigational hypomethylating agent; cytotoxic chemotherapy within 14 days of screening; concurrent use of erythropoiesis-stimulating agents, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor; or allogeneic stem cell transplant.

Of the 33 patients included the study, 14 had AML and 19 had MDS. Median age was 65, and 64% were men. About a third of patients had a Karnofsky performance status ≥90, and a majority had received reduced intensity conditioning.

Once patients had undergone HCT, they were re-screened 30 to 100 days post-transplant, and if considered eligible to initiate maintenance therapy, received the combination of eprenetapopt and azacitidine every 28 days for up to 12 cycles. The median number of treatment cycles was 7.

As of data cutoff, 31 of the 33 patients had discontinued treatment. The primary reasons for discontinuation were completion of 12 cycles of treatment (13 patients) and relapse (10 patients).

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