Agasti 2023: Ukwelashwa kweziguli ezikhulile ezine-acute myeloid leukemia (AML) esanda kutholakala ene-FLT3 internal tandem duplication (ITD) -positive, njengoba kutholwe ukuhlolwa okugunyazwe yi-FDA, nge-cytarabine evamile kanye ne-anthracycline induction kanye ne-cytarabine consolidation, kanye nokugcinwa i-monotherapy elandela ukuhlanganiswa kokwelashwa ngamakhemikhali, kugunyazwe i-Food and Drug Administration.
I-LeukoStrat CDx FLT3 Mutation Assay yaphinde yanikezwa imvume ye-FDA njengokuxilongwa komngane we-Vanflyta.
Ku-QuANTUM-First (NCT02668653), isilingo esilawulwa ngokungahleliwe, esingaboni kabili, esilawulwa yi-placebo esibandakanya iziguli ezingama-539 ezine-FLT3-ITD positive AML esanda kutholwa, ukuphumelela kwe-quizartinib kuhlanganiswe ne-chemotherapy kwahlolwa. A isivivinyo somtholampilo i-assay yasetshenziswa ukuze kutholwe isimo se-FLT3-ITD ngokuzayo, futhi i-LeukoStrat CDx FLT3 Mutation Assay engumngane yasetshenziswa ukuze ikuqinisekise ngemva kweqiniso.
Ngokusho kwesabelo sokuqala, iziguli zazingahleliwe (1: 1) ukuze zithole i-quizartinib (n = 268) noma i-placebo (n = 271) nge-induction, ukuhlanganiswa, nokugcinwa kwe-monotherapy. Ekuqaleni kokwelashwa kwangemva kokuhlanganisa, kwakungekho ukuphinda kwenziwe okungahleliwe. Ngemva kokululama kwe-hematopoietic stem cell transplantation (HSCT), iziguli ezathola i-HSCT zaqala ukwelashwa kwesondlo.
Ukusinda sekukonke (i-OS), okubalwe kusukela ngedethi ye-randomization kuze kube sekufeni kusuka kunoma iyiphi imbangela, kusetshenziswe njengesilinganiso esiyinhloko somphumela wokusebenza ngempumelelo. Ngemva kokudlula okungenani izinyanga ze-24 kusukela isiguli sokugcina sabelwe ngokungahleliwe, ukuhlaziywa okukhulu kwenziwa. Esivivinyweni, ingalo ye-quizartinib ibonise ukwenyuka okuphawulekayo kwe-OS [ingozi yesilinganiso (HR) 0.78; 95% CI: 0.62, 0.98; 2 okuhlangothini p=0.0324]. Ngesikhathi esimaphakathi sezinyanga ezingama-38.6 (95% CI: 21.9, NE), izinga le-CR yengalo ye-quizartinib lalingu-55% (95% CI: 48.7, 60.9), futhi isilinganiso se-CR yeqembu le-placebo sasingu-55% (95% CI: 49.2 , 61.4) enobude obumaphakathi bezinyanga eziyi-12.4 (95% CI: 8.8, 22.7).
Ukulandela i-allogeneic HSCT, i-quizartinib ayinconywa njenge-monotherapy yesondlo. I-Quiartinib ayizange iboniswe ukwandisa i-OS kulesi simo.
Ukwelulwa kwe-QT, ama-torsades de pointes, nokuboshwa kwenhliziyo konke kubalulwe esixwayiso esisebhokisini se-quizartinib. I-Vanflyta REMS kuphela, uhlelo olukhawulelwe ngaphansi Kwesu Lokuhlola Ubungozi kanye Nesu Lokunciphisa (REMS), olunikeza i-quizartinib. Ukuze uthole uhlu olubanzi lwemiphumela emibi, bheka ulwazi olunqunyiwe.
Umthamo onconyiwe we-quizartinib umi kanje:
- Ukungeniswa: 35.4 mg ngomlomo kanye ngosuku ngezinsuku ze-8-21 ze-"7 + 3" (cytarabine [100 noma 200 mg/m2/day] ngezinsuku 1 kuya ku-7 kanye ne-daunorubicin [60 mg/m2/day] noma i-idarubicin [12 mg /m2/usuku] ngezinsuku 1 kuya kwezi-3) nangezinsuku ezingu-8-21 noma ezingu-6-19 zokungeniswa kwesibili kokuzithandela (“7 + 3” noma “5 + 2” [izinsuku ezingu-5 ze-cytarabine kanye nezinsuku ezingu-2 ze-daunorubicin noma i-idarubicin], ngokulandelana),
- b) Ukuhlanganiswa: 35.4 mg ngomlomo kanye ngosuku ngezinsuku ezingu-6-19 zomthamo ophezulu we-cytarabine (1.5 kuya ku-3 g/m2 njalo ngamahora angu-12 ngezinsuku 1, 3 kanye no-5) kuze kube imijikelezo e-4, futhi
- c) Isondlo: 26.5 mg ngomlomo kanye ngosuku Ezinsukwini 1 kuya ku-14 kanye ne-53 mg kanye ngosuku, ngemva kwalokho, kuze kufike emijikelezweni yezinsuku ezingu-28 ezingamashumi amathathu nesithupha.
Buka imininingwane egcwele ye-Vanflyta
