Novel Drug-Chemotherapy Combo After Stem Cell Transplant Associated With ‘Favorable Survival Outcomes’ in Group of Rare Blood Cancers


The findings support future studies of assessing the safety and efficacy of the novel drug-chemotherapy combination as a maintenance strategy following stem cell transplantation across a range of blood cancers, according to the study authors.

Maintenance treatment with eprenetapopt, a novel drug, plus the chemotherapy Vidaza (azacitidine) following allogeneic hematopoietic stem cell transplantation was associated with improved survival outcomes in a group of patients with TP53-mutant, high-risk acute myeloid leukemia and myelodysplastic syndromes, according to new study findings.

Disease relapse is the primary reason why allogeneic hematopoietic stem cell transplants fail, according to the study authors, who noted that novel strategies for stem cell transplant to reduce the risk for disease relapse are severely needed.

Of note, an allogeneic hematopoietic stem cell transplant is a procedure where a patient with cancer receives healthy blood-forming stem cells from a donor to replace their own stem cells that have been damaged by other cancer treatments such as radiation or chemotherapy.

“Currently, maintenance strategies (which are used to reduce the risk for disease recurrence) are not standard of care in allogeneic (hematopoietic stem cell transplant) for (acute myeloid leukemia and myelodysplastic syndromes),” the study authors wrote.

In preclinical trials, eprenetapopt — a small molecule drug that may reactivate mutant p53 proteins — was active alongside Vidaza. Moreover, results from prior studies have shown the combination to be safe and effective in patients with other forms of blood cancers.

As a result, investigators aimed to see if maintenance therapy with eprenetapopt and Vidaza would induce similar results in this high-risk patient population.

They conducted a phase 2, multicenter trial to analyze if post-transplant eprenetapopt plus Vidaza improved relapse-free survival (which is the length of time following completion of primary treatment that a patient survives without signs or symptoms of that cancer). Based on prior results, the study investigators determined that a one-year relapse-free survival rate of 50% or greater would be considered successful.

A total of 84 patients were screened to determine if they were eligible for an allogeneic hematopoietic stem cell transplantation. Of the 55 patients who received a transplant, 33 patients (14 with acute myeloid leukemia and 19 with myelodysplastic syndromes) received maintenance treatment with eprenetapopt and Vidaza.

At a median follow-up of 14.5 months, maintenance therapy was associated with a median relapse-free survival of 12.5 months and an estimated one-year relapse-free survival rate of 59.9%. Additionally, the median overall survival (time from treatment to death of any cause) was 20.6 months at a median follow-up of 17 months. It was also estimated that the one-year overall survival rate was 78.8%.

Some of the most frequent severe or worse side effects to occur in the patient population included a decrease in white blood cell count (36%), anemia (27%) and hypertension (12%). There were four serious cases of fever and two serious cases each of febrile neutropenia (fever during a period of low white blood cell count) and difficult or labored breathing.

There were some occurrences of dose reduction (9%), interruption (6%) or delay (6%) because of treatment-related side effects.

Two patient deaths were reported during the study period — one that was associated with a side effect not related to study treatment and one attributed to disease progression more than 30 days after study treatment completion.

“TP53 mutation is associated with a poor prognosis in (acute myeloid leukemia) and (myelodysplastic syndromes), even in patients who undergo allogeneic (hematopoietic stem cell transplantation),” the study authors wrote. “Post-(hematopoietic stem cell transplantation) maintenance therapy with eprenetapopt plus (Vidaza) in this high-risk population of patients with TP53 mutant (acute myeloid leukemia) or (myelodysplastic syndromes) led to favorable survival outcomes. These data support future exploration of this maintenance strategy in a phase 3 … study of eprenetapopt plus (Vidaza) versus placebo plus (Vidaza) in patients with TP53 mutant myeloid malignancies.”

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