Gilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors
dc.contributor.author | Numan, Yazan | |
dc.contributor.author | Abdel Rahman, Zaid | |
dc.contributor.author | Grenet, Justin | |
dc.contributor.author | Boisclair, Stephanie | |
dc.contributor.author | Bewersdorf, Jan Philipp | |
dc.contributor.author | Collins, Cailin | |
dc.contributor.author | Barth, Dylan | |
dc.contributor.author | Fraga, Martina | |
dc.contributor.author | Bixby, Dale L. | |
dc.contributor.author | Zeidan, Amer M. | |
dc.contributor.author | Yilmaz, Musa | |
dc.contributor.author | Desai, Pankil | |
dc.contributor.author | Mannis, Gabriel | |
dc.contributor.author | Deutsch, Yehuda E. | |
dc.contributor.author | Abaza, Yasmin | |
dc.contributor.author | Dinner, Shira | |
dc.contributor.author | Frankfurt, Olga | |
dc.contributor.author | Litzow, Mark | |
dc.contributor.author | Al-Kali, Aref | |
dc.contributor.author | Foran, James M. | |
dc.contributor.author | Sproat, Lisa Z. | |
dc.contributor.author | Jovanovic, Borko | |
dc.contributor.author | Daver, Naval | |
dc.contributor.author | Perl, Alexander E. | |
dc.contributor.author | Altman, Jessica K. | |
dc.date.accessioned | 2022-03-07T03:11:32Z | |
dc.date.available | 2023-04-06 22:11:31 | en |
dc.date.available | 2022-03-07T03:11:32Z | |
dc.date.issued | 2022-03-01 | |
dc.identifier.citation | Numan, Yazan; Abdel Rahman, Zaid; Grenet, Justin; Boisclair, Stephanie; Bewersdorf, Jan Philipp; Collins, Cailin; Barth, Dylan; Fraga, Martina; Bixby, Dale L.; Zeidan, Amer M.; Yilmaz, Musa; Desai, Pankil; Mannis, Gabriel; Deutsch, Yehuda E.; Abaza, Yasmin; Dinner, Shira; Frankfurt, Olga; Litzow, Mark; Al-Kali, Aref ; Foran, James M.; Sproat, Lisa Z.; Jovanovic, Borko; Daver, Naval; Perl, Alexander E.; Altman, Jessica K. (2022). "Gilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors." American Journal of Hematology 97(3): 322-328. | |
dc.identifier.issn | 0361-8609 | |
dc.identifier.issn | 1096-8652 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/171831 | |
dc.description.abstract | Gilteritinib is approved for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with an FLT3- mutation (FLT3mut+). However, the gilteritinib phase 3 ADMIRAL study (Perl et al NEJM 2019) was conducted prior to widespread adoption of either midostaurin as a component of standard intensive induction and consolidation or posttransplant FLT3 inhibitor maintenance. We performed a retrospective analysis using data from 11 US centers and where we identified 113 patients who received gilteritinib alone or as combination therapy for the treatment of R/R FLT3mut+ AML. The composite complete remission (CR) rate (CRc, defined as CR- +- CRi- +- CR with incomplete platelet recovery [CRp]) was 48.7% (n = 55). The CRc rate after treatment with gilteritinib in patients who were treated with only prior 7+3 and midostaurin with or without consolidation was 58% with a median survival of 7.8 months. Survival was longest in patients who obtained a CR, particularly a cMRD (clinical minimal or measurable residual disease) negative response; this remained significant after censoring at the time of stem cell transplant. The mitogen- activated protein kinase pathway activating mutations that are known for gilteritinib resistance (NRAS, KRAS, and PTPN11) had lower CRc (35% vs. 60.5%) and lower median overall survival than patients’ whose leukemia did not express these mutations (4.9 months vs. 7.8 months) (HR 2.4; 95% CI 1. 5.4) p value <.01. | |
dc.publisher | John Wiley & Sons, Inc. | |
dc.title | Gilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors | |
dc.type | Article | |
dc.rights.robots | IndexNoFollow | |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | |
dc.subject.hlbsecondlevel | Oncology and Hematology | |
dc.subject.hlbtoplevel | Health Sciences | |
dc.subject.hlbtoplevel | Science | |
dc.description.peerreviewed | Peer Reviewed | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/171831/1/ajh26447_am.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/171831/2/ajh26447.pdf | |
dc.identifier.doi | 10.1002/ajh.26447 | |
dc.identifier.source | American Journal of Hematology | |
dc.identifier.citedreference | Miller CA, Wilson RK, Ley TJ. Genomic landscapes and clonality of de novo AML. N Engl J Med. 2013; 369 ( 15 ): 1473. | |
dc.identifier.citedreference | Ding L, Ley TJ, Larson DE, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole- genome sequencing. Nature. 2012; 481 ( 7382 ): 506. | |
dc.identifier.citedreference | Man CH, Fung TK, Ho C, et al. Sorafenib treatment of FLT3- ITD + acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. Blood. 2012; 119 ( 22 ): 5133 - 5143. | |
dc.identifier.citedreference | Smith CC, Wang Q, Chin CS, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature. 2012; 485 ( 7397 ): 260 - 263. | |
dc.identifier.citedreference | 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. | |
dc.identifier.citedreference | Rashidi A, Walter RB, Tallman MS, Appelbaum FR, DiPersio JF. Maintenance therapy in acute myeloid leukemia: an evidence- based review of randomized trials. Blood. 2016; 128 ( 6 ): 763 - 773. | |
dc.identifier.citedreference | Burchert A, Bug G, Fritz LV, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3- internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020; 38 ( 26 ): 2993 - 3002. | |
dc.identifier.citedreference | Maziarz RT, Fernandez H, Patnaik MM, et al. Radius: midostaurin (mido) plus standard of care (SOC) after allogeneic stem cell transplant (alloSCT) in patients (pts) with FLT3- internal tandem duplication (ITD)- mutated acute myeloid leukemia (AML). Biol Blood Marrow Transplant. 2019; 25 ( 3 ): S11 - S12. | |
dc.identifier.citedreference | Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017; 377 ( 5 ): 454 - 464. | |
dc.identifier.citedreference | Schlenk RF, Döhner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008; 358 ( 18 ): 1909 - 1918. | |
dc.identifier.citedreference | Luskin MR, Lee JW, Fernandez HF, et al. Benefit of high- dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016; 127 ( 12 ): 1551 - 1558. | |
dc.identifier.citedreference | Choudhary C, Schwäble J, Brandts C, et al. AML- associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations. Blood. 2005; 106 ( 1 ): 265 - 273. | |
dc.identifier.citedreference | Santos FP, Jones D, Qiao W, et al. Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia. Cancer. 2011; 117 ( 10 ): 2145 - 2155. | |
dc.identifier.citedreference | Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017; 129 ( 4 ): 424 - 447. | |
dc.identifier.citedreference | Schmalbrock LK, Dolnik A, Cocciardi S, et al. Clonal evolution of acute myeloid leukemia with FLT3- ITD mutation under treatment with midostaurin. Blood. 2021; 137: 3093 - 3104. | |
dc.identifier.citedreference | Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003; 21 ( 24 ): 4642 - 4649. | |
dc.identifier.citedreference | Tarver TC, Hill JE, Rahmat L, et al. Gilteritinib is a clinically active FLT3 inhibitor with broad activity against FLT3 kinase domain mutations. Blood Adv. 2020; 4 ( 3 ): 514 - 524. | |
dc.identifier.citedreference | Heidel F, Solem FK, Breitenbuecher F, et al. Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn- 676 in the FLT3 tyrosine kinase domain. Blood. 2006; 107 ( 1 ): 293 - 300. | |
dc.working.doi | NO | en |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.