San Diego, CA—More than 40% of older patients with acute myeloid leukemia (AML) associated with an IDH2 mutation achieved complete remission when treated with the IDH2 inhibitor enasidenib (Idhifa), according to results of a mutation-driven clinical trial substudy presented at ASH 2018.
Overall, 12 of 27 patients attained complete remission, including 2 patients who had incomplete hematologic recovery. No early deaths occurred, and the treatment was generally well tolerated.
“In patients older than 60, enasidenib monotherapy is safe and effective,” said Eytan M. Stein, MD, Hematologic Oncologist, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York City.
“Differentiation syndrome is the most common serious adverse event and needs to be treated with steroids,” he added.
Personalized Medicine Clinical Trial
The findings are early results from a subprotocol of the Beat AML Master Trial for older patients (aged 62-84 years) with untreated AML. Sponsored by the Leukemia & Lymphoma Society, the Beat AML Master Trial is a personalized medicine clinical trial and its overall objective is the evaluation of novel therapies chosen on the basis of mutations identified by next-generation sequencing in patients with untreated AML.
“The primary objective of the Master Trial protocol is to determine the feasibility of assigning AML patients to the subprotocol treatment arms, based on next-generation sequencing that is done within 7 days from the receipt of samples at the central lab,” Dr Stein said, noting that the goal is “to prove that you can do a precision medicine trial in a group of patients where many people think they need to be treated quite rapidly.”
“Patients are assigned to treatment by [a biologic] marker,” said Dr Stein. “If they are marker-positive, they go on to a targeted agent or a combination. If they are marker-negative, they go on to a novel agent that is nontargeted,” he added.
The Beat AML Master Trial Subprotocol
Dr Stein reported findings from a subprotocol for patients with AML and IDH2 mutation that was confirmed by next-generation sequencing. All patients began treatment with enasidenib monotherapy and continued for a maximum of 4 cycles. Patients who achieved a complete remission, including remission with incomplete recovery, continued therapy with enasidenib until disease progression.
All other patients (ie, those who did not achieve complete remission) continued treatment with enasidenib plus azacitidine (Vidaza).
The study’s primary objective was overall response rate. The patients’ median age was 76 years, a majority of them had normal karyotype, and the proportion of IDH2 R140 or IDH2 R172 mutation was 78% (N = 18) versus 22% (N = 5).
The results showed an overall response rate of 44.4%, a rate that is at least comparable to the results observed in other studies involving patients with relapsed or refractory AML. The remaining 15 patients had less than complete response, including partial response and stable disease. Of these 15 patients, 9 continued treatment with enasidenib plus azacitidine.
Only 1 of 6 patients with concurrent RAS pathway and IDH2 mutations achieved remission. Dr Stein said that novel combination therapies for patients with concurrent RAS and IDH2 mutations are being investigated and developed within the Beat AML Master Trial.
A summary of the most frequent adverse events showed that 6 (21.4%) patients had a differentiation syndrome, which resolved in all cases with systemic steroid therapy.
Other frequent (≥5% of patients) adverse events were sepsis in 4 (14.3%) patients and 2 (7.1%) cases each of pneumonia, cellulitis, increased bilirubin, and pyrexia.