Findings from a randomized trial, published in The Lancet Oncology, showed that combining enasidenib with azacitidine was well tolerated and significantly improved overall response rates (ORR) in patients with newly diagnosed, mutant-IDH2 acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy versus treatment with azacitidine alone. According to the study’s lead author, Courtney DiNardo, MD, their results suggest that clinical outcomes in this patient population could be improved with the combination therapy.
The study’s participants were aged 18 years or older and had an Eastern Cooperative Oncology Group (ECOG) performance status of zero to two. They were randomly assigned (2:1) to an enasidenib plus azacitidine group, or an azacitidine-only group, and arranged by acute myeloid leukemia subtype (de novo or secondary). The primary outcome was the ORR at a prespecified interim analysis once all patients had undergone at least one year of follow-up.
Sixty-eight patients were given enasidenib plus azacytidine, while 33 were given only azacitidine. A total of 50 patients (74%, 95% confidence interval (CI), 61–84) in the enasidenib plus azacitidine group and 12 (36%, 95% CI 20–55) patients in the azacitidine group achieved an overall response (odds ratio [OR] = 4.9, 95% CI, 2.0–11.9, p = 0.0003).
Common treatment-related grade III or IV adverse events and their incidence between the groups included thrombocytopenia (combination group = 25 of 68 [37%] vs. monotherapy group = 6 of 32 [19%]), neutropenia (25 [37%] vs. 8 [25%]), anemia (13 [19%] vs. 7 [22%]), and febrile neutropenia (11 [16%] vs. 5 [16%]).
The rate of serious treatment-related adverse events was similar between the groups and included febrile neutropenia (combination group = 9 [13%] vs. monotherapy group = 5 [16%]), differentiation syndrome (7 [10%] vs. 0), and pneumonia (3 [4%] vs. 2 [6%]). No deaths related to the treatments were reported.
The researchers ultimately suggested that the combination of enasidenib plus azacitidine appeared to show significant advantages versus azacitidine alone in this patient population while being well tolerated.