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

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.

• 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
• Journal: Blood cancer journal (Blood Cancer J) Vol. 12 Issue 5 Pg. 84 (05 30 2022) ISSN: 2044-5385 [Electronic] United States
• PMID: 35637252 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Aniline Compounds
• Protein Kinase Inhibitors
• Pyrazines
• gilteritinib
• Sorafenib
• FLT3 protein, human
• fms-Like Tyrosine Kinase 3
• Staurosporine
• midostaurin

Topics

• Aniline Compounds
• Humans
• Leukemia, Myeloid, Acute (drug therapy, genetics)
• Mutation
• Protein Kinase Inhibitors (adverse effects)
• Pyrazines
• Retrospective Studies
• Sorafenib (pharmacology, therapeutic use)
• Staurosporine (analogs & derivatives)
• fms-Like Tyrosine Kinase 3 (genetics)