The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Hematology Advisor‘s conference coverage.

Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have received prior treatment with the tyrosine kinase inhibitors (TKI) midostaurin or sorafenib may achieve remission with gilteritinib, according to study results presented by Alexander E. Perl, MD, of the University of Pennsylvania in Philadelphia, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.1

Furthermore, heavily pretreated patients with FLT3-mutated AML in the CHRYSALIS trial ( Identifier: NCT02014558) who received prior treatment with TKIs were able to achieve high response rates with gilteritinib.2

Following up on results from the phase 1/2 CHRYSALIS trial and phase 3 ADMIRAL trial ( Identifier:  NCT02141939), the investigators aimed to determine whether prior TKI therapy affected response and survival in these 2 trials.2,3

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“Despite enrollment of over 400 patients with FLT3-mutated AML to these trials, the efficacy of gilteritinib in patients previously treated with a [TKI], specifically, midostaurin or sorafenib, is unclear,” said Dr Perl.

Dr Perl and colleagues retrospectively examined clinical outcomes in patients with R/R AML who were previously treated with midostaurin or sorafenib prior to receiving gilteritinib in the CHRYSALIS trial (120 or 200 mg) or the ADMIRAL trial (120 mg); patients who had been randomly assigned to salvage chemotherapy in the ADMIRAL trial were also included. FLT3-mutated AML included FLT3-internal tandem duplication (ITD) only, FLT3-tyrosine kinase domain (TKD) only, and FLT3-ITD and FLT3-TKD.

Of the 145 patients with FLT3-mutated AML who received gilteritinib in the CHRYSALIS trial, 33 (23%) had undergoing prior treatment with a TKI (median age, 56 years) and 112 had not (median age, 61 years). Of the patients with FLT3-mutated AML in the ADMIRAL trial, 13% (31/247) of patients in the gilteritinib arm and 11% (14/124) of patients in the salvage chemotherapy arm had received prior treatment with TKIs. Baseline demographics and disease characteristics across arms and trials were similar. Although most patients in the CHRYSALIS trial had received 2 or more lines of prior AML therapy, those in the ADMIRAL trial had received only 1 line of prior AML therapy.

Rates of composite complete remission (CRc; defined as the sum of patients who achieved complete remission [CR], CR with incomplete hematologic recovery, and CR with incomplete platelet recovery) were similar in gilteritinib-treated patients who had undergone treatment with TKIs and those who had not received TKI therapy (CHRYSALIS, 42% and 43%, respectively; ADMIRAL, 48% and 55%, respectively). Lower CRc rates were observed in the salvage chemotherapy arm regardless of prior TKI therapy status (prior TKI, 21%; no prior TKI, 22%).

Data from the CHRYSALIS study showed that in patients with FLT-ITD mutations alone (prior TKI, 41%; no prior TKI, 46%) and in patients with FLT3-ITD and FLT3-TKD mutations (prior TKI, 50%; no prior TKI, 57%), high response rates were achieved regardless of prior TKI treatment status.

Data from the ADMIRAL trial demonstrated high CRc rates in patients with FLT3-ITD (prior TKI, 41%; no prior TKI, 57%), FLT3-TKD (prior TKI, 60%; no prior TKI, 38%), or both FLT3-ITD and -TKD (prior TKI, 75%; no prior TKI, 67%) in the TKI status subgroups from the gilteritinib arm.

In the CHRYSALIS trial, median overall survival (OS) was similar among the groups regardless of prior TKI therapy; however, long-term survival was more common among patients who had not received previous TKI therapy. In addition, FLT3-mutation type did not seem to affect the overall duration. Conversely, in the ADMIRAL trial, among patients who had received prior treatment with a TKI, those treated with gilteritinib had a longer median OS survival compared with those treated with salvage chemotherapy (6.5 mo vs 4.7 mo; hazard ratio, 0.625, 95% CI, 0.47-0.824; nominal P =.0008).

In a combined analysis of both trials, similarly high CRc rates were achieved in patients treated with gilteritinib who had or had not undergone prior treatment with TKIs (45% and 51%, respectively). Median OS appeared to trend toward patients who had not undergone prior treatment with TKIs compared with those who had (8.7 and 7.0 mo, respectively).

“Patients with FLT3-mutated R/R AML who received prior midostaurin or sorafenib achieved high remission rates with gilteritinib, including heavily pretreated patients,” concluded Dr Perl.

Limitations include small sample sizes among some of the subgroups and the retrospective nature of the study.

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Read more of Hematology Advisor’s coverage of the ASH 2020 meeting by visiting the conference page.


  1. Perl AE, Altman JK, Hosono N, et al. Clinical outcomes in patients with relapsed/refractory acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 334.
  2. Perl AE, Altman JK, Cortes J, et al. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol. 2017;18(8):1061-1075. doi:10.1016/S1470-2045(7)30416-3
  3. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019;381(18):1728-1740. doi:10.1056/NEJMoa1902688