Addition of Sorafenib to Standard Chemotherapy in Pediatric Patients With High Allelic Ratio FLT3-ITD–Positive AML

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In an analysis from the Children’s Oncology Group protocol AAML1013 reported in the Journal of Clinical Oncology, Pollard et al found that the addition of sorafenib to standard chemotherapy may benefit pediatric patients with high allelic ratio FLT3-ITD–positive acute myeloid leukemia (AML).

Study Details

Initial investigation in 12 patients established the maximum tolerated dose of sorafenib as 200 mg/m2 once daily in induction therapy; dose-limiting toxicities included rash (one case of grade 3 and one case of grade 2), grade 2 hand-foot syndrome, and grade 3 fever. The current analysis compared outcomes in a group of 72 patients treated with sorafenib at 200 mg/m2 once daily added to standard chemotherapy and used as maintenance therapy (100 mg/m2) with those in a cohort of 76 patients who received identical chemotherapy without sorafenib.  

Key Findings

Outcomes were improved in the sorafenib group vs the sorafenib-unexposed group, including:

  • A significantly higher rate of complete remission at end of induction 1 (75% vs 57%, P = .028)
  • Numerically improved 3-year overall survival from study entry (65.8% vs 55.3%, P = .244)
  • Significantly improved 3-year event-free survival from entry (55.9% vs 31.9%, P = .001)
  • Significantly improved 3-year disease-free survival (70.9% vs 49.4%, P = .032) and risk of relapse (17.6% vs 44.1%, P = .012) from end of induction 1 in patients with complete remission.

However, hematopoietic stem cell transplantation (HSCT) was received by 64% of the sorafenib group vs 25% of the sorafenib-unexposed group (P< .001). In multivariate analysis including HSCT and favorable co-occurring mutations, the sorafenib-unexposed group had significantly poorer event-free survival from entry (hazard ratio [HR] = 2.37, 95% confidence interval [CI] = 1.45–3.88, P < .001), disease-free survival from complete remission (HR = 2.28, 95% CI = 1.08–4.82, P = .032), and relapse risk from complete remission (HR = 3.03, 95% CI = 1.31–7.04, P = .010). No significant difference in overall survival was observed (HR = 1.21, 95% CI = 0.67–2.20, P = .525).

The investigators concluded, “Sorafenib can be safely added to conventional AML chemotherapy and may improve outcomes in pediatric high allelic ratio [FLT3-ITD–positive] AML.”

Jessica A. Pollard, MD, of Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute and St. Baldrick’s Foundation. For full disclosures of the study authors, visit

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