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Rebecca Olin, MD, MS


Combining Sorafenib With Conventional Chemotherapy to Treat Pediatric FLT3-Mutant AML

By: Gavin Calabretta, BS
Posted: Wednesday, August 17, 2022

In pediatric acute myeloid leukemia (AML), high allelic ratio FLT3 internal tandem duplication (FLT3/ITD) mutations occur in approximately 10% to 15% of patients and are indicators of poor prognosis. Observing early success with the tyrosine kinase inhibitor sorafenib in treating pediatric AML, Jessica A. Pollard, MD, of Dana-Farber Cancer Institute, Boston, and colleagues analyzed the clinical potential of combining sorafenib with standard chemotherapy in a randomized phase III trial (AAML1031) led by the Children’s Oncology Group. The data, published in the Journal of Clinical Oncology, suggest the treatment regimen may effectively inhibit FLT3 expression while additionally improving survival outcomes in this patient population.

“Pediatric high allelic ratio FLT3/ITD acute myeloid leukemia is a high-risk disease subset,” the researchers remarked. “For treatment of pediatric FLT3/ITD acute myeloid leukemia outside of a study context, these data provide compelling support for sorafenib combined with conventional chemotherapy.”

The study incorporated three cohorts. The first involved an initial safety phase, which determined a maximum tolerated daily dose of 200 mg/m2. The second and third cohorts tested sorafenib in induction and as a single-agent maintenance therapy, respectively. Evaluating clinical outcomes, the investigators compared 72 patients from the second and third cohorts with 76 individuals who had previously received identical chemotherapy without sorafenib.

Reportedly, patients treated with sorafenib achieved significantly longer event-free survival (hazard ratio [HR] = 2.37, 95% confidence interval [CI] = 1.45–3.88, P < .001) and disease-free survival (HR = 2.28, 95% CI = 1.08–4.82, P = .032) with a lower relapse risk (HR = 3.03, 95% CI = 1.31–7.04, P = .010). In addition, plasma inhibitory analysis revealed that sorafenib produced a median trough FLT3 inhibition of 92%, 91%, and 81% during the first three courses of therapy. This clinical benefit was independent of NMP1 mutation status or previous hematopoietic stem cell transplantation.

Disclosure: For full disclosures of the study authors, visit

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