Rare Disease Report

Overall Survival Improved in AML Patients by Gilteritinib

JUNE 06, 2017
Mathew Shanley
New data concludes that molecular responses to gilteritinib directly correlated with clinical response and improved overall survival (OS) in patients with FLT3 mutation-positive (FLT3mut+) relapsed/refractory (R/R) acute myeloid leukemia (AML).
This is the first-ever demonstration of molecular response to a FLT3 inhibitor in AML, and these data, presented at the 2017 American Society of Clinical Oncology (ASCO 2017) annual meeting in Chicago by Jessica K. Altman, et al., propose ITD signal ratio could predict durable clinical benefit of gilteritinib.
Antileukemic activity in FLT3 mutation-positive (FLT3mut+) relapsed/refractory (R/R) AML in the CHRYSALIS Phase I/II study (NCT02014558) was displayed by the drug, a highly selective FLT3/AXL inhibitor, specifically at doses ≥80 mg/d. This investigative examination measured molecular response to gilteritinib in a CHRYSALIS subpopulation.
Eighty of the 147 FLT3-ITDmut+ patients who received gilteritinib 120 or 200 mg/d were included in this analysis, and composite response rate for the patients was 55%. Twenty patients (25%) had an ITD signal ratio of ≤10−2 during response, and of the 20 patients, 18 had a ratio of ≤10−3 (major molecular response [MMR]) and 13 had a ratio of ≤10−4 (minimal residual disease [MRD] negative).
The study spanned 26 locations, and eligibility for patients involved included age (18 years and older), all sexes and no healthy volunteers were permitted. Inclusion criteria included the subject’s being defined as morphologically documented primary or secondary AML by the World Health Organization criteria, and at least one of the following:

  • Refractory to at least 1 cycle of induction chemotherapy
  • Relapsed after achieving remission with a prior therapy
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Subject's interval from prior treatment to time of study drug administration is at least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast cells), or at least 5 half-lives for prior experimental agents or noncytotoxic agents.
  • Subject must meet the following criteria as indicated on the clinical laboratory tests*:
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x institutional upper limit normal (ULN)
  • Total serum bilirubin < 1.5x institutional ULN
  • Serum creatinine < 1.5 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
  • Subject agrees not to participate in another interventional study while on treatment.

Average time to achieve the smallest signal ratio was 54 days, and 80% of patients with ITD signal ratios <10−2 saw complete elimination of morphologic leukemia. Patients who had a signal ratio ≤10−2, MMR, or were MRD negative had considerably longer median OS than those who did not (Table 1).

The estimated completion date of the study is December 1, 2017. Clinical trial information can be found at clinicaltrials.gov.

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