Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib
Year: 2022
Type: article
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.
Source: Blood Cancer Journal
Authors: Alexander E. Perl, Naoko Hosono, Pau Montesinos, Nikolai Podoltsev, Giovanni Martinelli, Nicki Panoskaltsis, Christian Recher, Catherine C. Smith, Mark J. Levis, Stephen Strickland, Christoph Röllig, Marco Groß-Langenhoff, Wen-Chien Chou, Je-Hwan Lee, Hisayuki Yokoyama, Nahla Hasabou, Qiaoyang Lu, Ramon V. Tiu, Jessica K. Altman
Institutions: Abramson Cancer Center, University of Pennsylvania, University of Fukui, Hospital Universitari i Politècnic La Fe, Yale University, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Emory University, Winship Cancer Institute, Centre de Recherches en Cancérologie de Toulouse, University of California, San Francisco, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Vanderbilt University, Vanderbilt-Ingram Cancer Center, University Hospital Carl Gustav Carus, Astellas Pharma (Germany), National Taiwan University Hospital, Asan Medical Center, University of Ulsan, Tohoku University, Sendai Medical Center, National Hospital Organization, Astellas Pharma (United States), Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,590
OpenAlex ID: W4281622146