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.
| Original language | English (US) |
|---|---|
| Article number | 84 |
| Journal | Blood cancer journal |
| Volume | 12 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2022 |
Funding
AE Perl reports grants, personal fees and non-financial support from Astellas, during the conduct of the study; grants, personal fees, and non-financial support from FujiFilm; grants, personal fees, and non-financial support from Daiichi Sankyo; grants and personal fees from Abbvie and Actinium Pharmaceuticals; personal fees from Agios, Loxo, LLS/Beat AML, and Forma; non-financial support from Arog; personal fees and non-financial support from New Link Genetics, Novartis, Takeda, and Jazz; and grants from Bayer and Biomed Valley Discoveries, outside the submitted work. N Hosono reports no relevant conflicts of interest to disclose. P Montesinos reports research support from Pfizer, Abbvie, and Daiichi Sankyo; consultancy from Celgene, Pfizer, and Abbvie; and speakers bureau from Astellas, Novartis, and Janssen. N Podoltsev reports consultancy fees from Pfizer, Celgene, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, Bristol-Myers Squibb, CTI Biopharma, PharmaEssentia, Constellation Pharmaceuticals, Cogent BioSciences, and AbbVie; and institutional research funding from Pfizer, Celgene, CTI Biopharma, Boehringer Ingelheim, Astellas, Daiichi Sankyo, Sunesis Pharmaceuticals, Jazz Pharmaceuticals, Astex Pharmaceuticals, Genentech, AI Therapeutics, Samus Therapeutics, Arog Therapeutics, and Kartos Therapeutics. G Martinelli reports grant funding and consultancy fees from Amgen, Ariad, Incyte, Pfizer, Roche, Celgene, Janssen, AbbVie, and Novartis. N Panoskaltsis reports no relevant conflicts of interest to disclose. C Recher reports grant funding and personal fees from Celgene, Sunesis, Amgen, and Novartis and personal fees from Incyte, Jazz Pharmaceuticals, AbbVie, Astellas, Macrogenics, and Otsuka. C Smith reports research funding from Abbvie, Revolution Medicines, Celgene, FujiFilm; consulting fees from Astellas, Daichi Sanyko, and Genentech to attend an advisory board meeting; and reports being a stockolder at Ligacept, LLC. MJ Levis reports grants and personal fees from Astellas and FujiFilm and personal fees from Daiichi Sankyo, Amgen, and Menarini. S Strickland reports consulting or advisory fees from Abbvie, Astellas Pharma, Jazz Pharmaceuticals, Kite, a Gilead company, Novartis, and Pfizer and research funding at an institutional level from Abbvie, Astellas Pharma, Inc, Celator/Jazz, Celgene, Daiichi Sankyo, Karyopharm Therapeutics, Menarini, Novartis, and Sunesis Pharmaceuticals. C R\u00F6llig has received grants from AbbVie, Novartis, and Pfizer; consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Janssen, Jazz, Novartis, Pfizer, and Roche; and honoraria for speaker engagements from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Janssen, Jazz, Novartis, Pfizer, and Roche. WC Chou reports no relevant conflicts of interest to disclose. H Lee has received honoraria for speaker engagements from AbbVie Korea and Astellas Korea, participated in and advisory board for AbbVie and Astellas, and is President of The Korean Society of Hematology. H Yokoyama reports having received honoraria from Astellas for speaking engagements. Q Lu, N Hasabou, M Gro\u00DF-Langenhoff are employees of Astellas. R Tiu is a former employee of Astellas. JK Altman reports advisory or consulting fees from AbbVie, Amgen, Astellas, Daiichi Sankyo, Kura Oncology, Syros, and Theradex; institutional research funding for trials conducted by ALX Oncology, Amgen, Aptos, Astellas, Aprea, BioSight, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, FujiFilm, Immunogen, Kartos, Kura Oncology, and Loxo; reimbursement for travel from BioSight; and serves on a data monitoring committee for GlycoMimetics. 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.
ASJC Scopus subject areas
- Hematology
- Oncology