Next-Generation Sequencing Could Help Treatment Decisions in Acute Myeloid Leukemia

August 2018 Vol 11, Special Issue - Leukemia Update
Chase Doyle

Chicago, IL—Next-generation sequencing (NGS) and novel targeted agents have transformed cancer care for several solid tumors and hematologic malignancies, but when it comes to acute myeloid leukemia (AML), results of a recent study suggest that these tools may be considerably underutilized.

The retrospective analysis of nearly 1500 patients with AML showed that NGS can positively affect therapy decisions in more than 30% of patients.

However, multiple barriers to clinical trial enrollment still exist for approximately 40% of patients with AML and actionable mutations.

"We believe that implementation of NGS in AML care is feasible, especially with such short reporting time," said lead investigator of the study, Rita Elias Assi, MD, Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX.

"We found that 66% of our patients harbor at least 1 potentially actionable mutation, and that opened the doors for broader targeting. NGS guided targeted therapy in more than 30% of patients, which resulted in an increased proportion of patients treated on targeted therapy over 4 years, as well as increased clinical trial accrual," Dr Assi reported at ASCO 2018.

"Most important, targeted therapy resulted in increased response rates and a potentially positive impact on relapse-free survival," Dr Assi added.

The advent of NGS has helped to identify a large number of recurrent somatic mutations that are important for therapy selection in different cancer types, including AML. Until recently, however, hypomethylating agents and cytarabine-based chemotherapy have been the only available mainstream treatments for AML associated with somatic mutations.

"Recent FDA approval of FLT3 and IDH inhibitors have challenged these strategies, but incorporation of these and other agents will require genomic annotation in clinical practice," she explained.

In August 2017, the FDA approved enasidenib (Idhifa), an IDH2 inhibitor, for patients with AML and IDH2 mutation. And in April 2017, the FDA approved the FLT3 inhibitor midostaurin (Rydapt), in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation, for patients with AML and FLT3 mutation. Other targeted therapies for AML are currently in clinical trials.

Study Details

The study by Dr Assi and colleagues was a single-center, retrospective cohort analysis that included 1470 consecutive adult patients with AML between October 2012 and May 2016.

The median time from NGS testing to results reporting was 9 days. Moreover, 80% (1183) of patients had their results reported within 2 weeks, and 37% (545) of patients received results within 1 week. Of all tested patients, 21% did not have any detectable mutations, said Dr Assi, but 66% of the patients had at least 1 mutation, with a median of 2 actionable mutations per patient.

"We found that patients who had actionable mutations were more likely to be treated on a clinical trial than those who did not have any actionable mutation, and the difference was statistically significant," said Dr Assi.

Targeted Therapies for Actionable Mutations

Of the 976 patients who had potentially actionable mutation, 36% received treatment in a clinical trial that did not include any targeted therapy, and only 25% received targeted therapy. Patients who received targeted therapy were more likely to have relapsed or refractory disease and were more likely to receive treatment early in clinical trials than those who did not receive targeted therapy, who were more likely to have newly diagnosed disease.

Most important, said Dr Assi, patients who received targeted therapy achieved higher overall response rates than those who did not receive such therapy, whether they were newly diagnosed or had relapsed or refractory disease. The use of targeted therapy also had a positive impact on relapse-free survival in patients with actionable mutations and tended to have positive impact on newly diagnosed disease.

Nevertheless, the large percentage of patients with actionable mutations who did not enroll in clinical trials left investigators keen on expanding the reach of precision medicine.

"This study shows that multiple barriers to clinical trial enrollment still exist in around 40% of patients with actionable mutations. This is where we still have room for improvement," Dr Assi concluded.

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Last modified: September 4, 2018
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