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CHICAGO -- Single-agent ivosidenib was well tolerated and resulted in deep and durable remissions in patients with relapsed or refractory acute myeloma leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation, according to a researcher here.

The rate of complete remission (CR) or CR with partial hematologic recovery (CRh) was 30.4% in these patients (95% CI, 22.5-39.3), reported Daniel Pollyea, MD, of the University of Colorado School of Medicine in Aurora, at the American Society of Clinical Oncology (ASCO) annual meeting.

"In this population of IDH-positive relapsed/refractory AML patients, ivosidenib was able to achieve durable responses," said Pollyea.

The true CR rate with ivosidenib (formerly AG-120) was 21.6%, with a median duration of response of 9.3 months (95% CI, 5.6-18.3) and median overall survival (OS) of 18.8 months in these patients.

In all, 41.6% of patients responded (95% CI, 32.9-50.8), with a 6.5-month median duration of response (95% CI, 4.6-9.3), according to the study, which was published simultaneously in the .

"In addition, patients were able to achieve transfusion independence," Pollyea said. Among 84 patients dependent on either red-cell or platelet transfusions (or both) at the start of treatment, 35% attained transfusion independence -- and fewer infectious complications were seen in these patients.

Of the 41 patients who were transfusion-independent at the start of treatment, more than half were able to maintain this for 56 days or more while on treatment.

In February 2018, the FDA accepted a (NDA), along with priority review, for ivosidenib for the treatment of patients with relapsed or refractory AML with IDH1 mutation. The agency is expected to make their decision later this year.

Following similar phase I data last year, the FDA approved the oral IDH2 inhibitor enasidenib (Idhifa) for relapsed or refractory AML patients with IDH2 mutations.

ASCO discussant Eunice Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, described ivosidenib as a "companion drug" for patients with IDH1-mutations.

IDH1 mutations are more rare than IDH2 mutations, occurring in roughly 6%-10% of AML patients compared with 9%-13%.

Wang told 番茄社区app that like enasidenib for IDH2-mutant AML, ivosidenib will likely become the next standard of care in IDH1-mutant AML. "I can't imagine the FDA would not approve the drug given the similarity of the data," she said, adding that AML patients will need to routinely be tested for IDH1/IDH2 mutations.

"I am hopeful that we'll have approval of AG-120, or ivosidenib, before the summer is out," said study co-author Courtney DiNardo, of MD Anderson Cancer Center in Houston.

In the clinic, DiNardo told 番茄社区app that she has seen "dramatic" responses to the drug firsthand, noting two patients she treated on the study who had durable responses of 1 to 2 years.

But Wang highlighted that more work needs to be done, citing the need for markers of resistance, whether they be co-mutations or otherwise. The study tested for the variant allele frequency of IDH1 mutations, and in 21% of CR/CRh patients, no residual IDH1 mutations were detectable on digital polymerase-chain-reaction assay. "So the drug is working, but we're not seeing massive eradication of that molecular marker," she said.

The next generation of IDH1 inhibitors, some of which are already undergoing dose-escalation studies, may be the solution to move treatment forward for these patients, Wang said.

The current study looked at data on 179 patients with relapsed and refractory IDH1-mutant AML who were part of a phase I dose-escalation and dose-expansion trial. Median patient age was 67. Evaluable patients (n=125) included those with relapsed or refractory disease who were treated with a 500-mg daily dose and had 6 months of follow-up. Most patients had primary AML (66%).

With a median follow-up of nearly 15 months, the median OS was 8.8 months in all comers, and 9.3 months for responders that did not achieve CR/CRh.

Overall 25.6% patients had a grade 3 or higher treatment-related adverse event, the most common of which were prolongation of the QT interval (7.0%), IDH differentiation syndrome (4.7%), anemia (2.3%), and thrombocytopenia (1.9%). Diarrhea, decreased platelet counts, hypoxia, febrile neutropenia, and leukocytosis each occurred in 1.2% of patients.

DiNardo highlighted IDH differentiation syndrome as a side effect to be aware of, but this can successfully be treated with steroids when found early, she said.

Ivosidenib and enasidenib are both currently being tested in the frontline setting with '7+3' chemotherapy for IDH1/IDH2-positive AML, and were presented at the 2017 American Society of Hematology annual meeting.