Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib

• Type of Material: Article
• Authors: Alexander E. Perl, University of Pennsylvania; Naoko Hosono, University of Fukui; Pau Montesinos, Hospital Universitario y Politécnico La Fe; Nikolai Podoltsev, Yale University; Giovanni Martinelli, Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” IRST S. r. l; Nicki Panoskaltsis, Emory University; Christian Recher, Cancer Research Center Toulouse; Catherine C. Smith, University of California San Francisco; Mark J. Levis, Johns Hopkins University; Stephen Strickland, Vanderbilt Ingram Cancer Center; Christoph Rollig, Univ Klinikum Carl Gustav Carus; Marco Gross-Langenhoff, Astellas Pharma GmbH; Wen-Chien Chou, National Taiwan University Hospital; Je-Hwan Lee, University of Ulsan; Hisayuki Yokoyama, National Hospital Organization Disaster Medical Center of Japan; Nahla Hasabou, Astellas Pharma US; Qiaoyang Lu, Astellas Pharma US; Ramon Tiu, Astellas Pharma US; Jessica K. Altman, Northwestern University
• Language: English
• Date: 2022-05-30
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41408-022-00677-7
• Title of Journal or Parent Work: Blood Cancer Journal
• Volume: 12
• Issue: 5
• Start Page: 84
• End Page: 84
• Grant/Funding Information: This study was funded by Astellas Pharma, Inc. Medical writing/editorial support was provided by Kalpana Vijayan, PhD, Elizabeth Hermans, PhD, and Cheryl Casterline, MA, from Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by the study sponsor.
• Keywords: Hematology; Inhibitor; D835 Mutations; Oncology; Resistance; Multicenter; Chemotherapy; Mechanisms; Life Sciences & Biomedicine; Science & Technology; FLT3
• Research Categories: Health Sciences, Rehabilitation and Therapy; Health Sciences, Health Care Management; Health Sciences, Oncology

Abstract

The fms-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib is indicated for relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML), based on its observed superior response and survival outcomes compared with salvage chemotherapy (SC). Frontline use of FLT3 tyrosine kinase inhibitors (TKIs) midostaurin and sorafenib may contribute to cross-resistance to single-agent gilteritinib in the R/R AML setting but has not been well characterized. To clarify the potential clinical impact of prior TKI use, we retrospectively compared clinical outcomes in patients with R/R FLT3-mutated AML in the CHRYSALIS and ADMIRAL trials who received prior midostaurin or sorafenib against those without prior FLT3 TKI exposure. Similarly high rates of composite complete remission (CRc) were observed in patients who received a FLT3 TKI before gilteritinib (CHRYSALIS, 42%; ADMIRAL, 52%) and those without prior FLT3 TKI therapy (CHRYSALIS, 43%; ADMIRAL, 55%). Among patients who received a prior FLT3 TKI in ADMIRAL, a higher CRc rate (52%) and trend toward longer median overall survival was observed in the gilteritinib arm versus the SC arm (CRc = 20%; overall survival, 5.1 months; HR = 0.602; 95% CI: 0.299, 1.210). Remission duration was shorter with prior FLT3 TKI exposure. These findings support gilteritinib for FLT3-mutated R/R AML after prior sorafenib or midostaurin.