2023-fevral: Zanubrutinib (Brukinsa, BeiGene USA, Inc.) FDA tomonidan surunkali limfotsitik leykemiya (CLL) yoki kichik limfotsitik limfoma (SLL) uchun tasdiqlangan.
SEQUOIA was used to assess effectiveness in CLL/SLL patients who had not received treatment (NCT03336333). A total of 479 patients were randomized 1:1 to receive either zanubrutinib until disease progression or unacceptable toxicity or bendamustine plus rituximab (BR) for 6 cycles in the randomized cohort that included patients without 17p deletion. Progression-free survival (PFS) was the primary efficacy outcome metric, as established by a separate review committee (IRC). In the zanubrutinib arm, the median PFS was not achieved (95% CI: NE, NE), but in the BR arm, it was 33.7 months (95% CI: 28.1, NE) (HR= 0.42, 95% CI: 0.28, 0.63; p=0.0001). For PFS, the estimated median follow-up was 25.0 months. Zanubrutinib was assessed in 110 patients with previously untreated CLL/SLL with a 17p deletion in a different non-randomized cohort of SEQUOIA. IRC reported an overall response rate (ORR) of 88% (95% CI: 81, 94). After a median follow-up of 25.1 months, the median duration of response (DOR) had not yet been attained.
ALPINE relapsli yoki refrakter CLL / SLL (NCT03734016) bo'lgan bemorlarda samaradorlikni baholadi. Hammasi bo'lib 652 ishtirokchi tasodifiy ravishda zanubrutinib yoki ibrutinibga tayinlangan. 1 oldingi davolash liniyalarining o'rtacha soni (1-8 oralig'i). IRC ma'lumotlariga ko'ra, ORR va DOR javoblarni tahlil qilishda ushbu nuqtada samaradorlikning asosiy natijalari bo'lgan. Zanubrutinib qo'li uchun ORR 80% (95% CI: 76, 85) va ibrutinib qo'li uchun 73% (95% CI: 68, 78) (javob tezligi nisbati: 1.10, 95% CI: 1.01, 1.20); p=0.0264). O'rtacha 14.1 oylik kuzatuvdan so'ng, hech bir qo'l o'rtacha DORga etib bormadi.
Zanubrutinibning eng ko'p uchraydigan nojo'ya ta'siri (30%) qon ketishi (42%), pastki nafas yo'llarining infektsiyasi (39%), trombotsitlar sonining kamayishi (34%), neytrofillar sonining kamayishi (42%) va mushak-skelet tizimining og'rig'i (30%). . Jismoniy shaxslarning 13 foizida teri bo'lmagan karsinomalar kabi ikkilamchi birlamchi malign o'smalar paydo bo'lgan. Bemorlarning 3.7 foizida atriyal fibrilatsiya yoki chayqalish, bemorlarning 0.2 foizida 3 yoki undan yuqori darajadagi qorincha aritmiyalari bor edi.
Kasallik kuchayguncha yoki chidab bo'lmas toksiklik mavjud bo'lgunga qadar, zanubrutinibning tavsiya etilgan dozasi kuniga ikki marta og'iz orqali qabul qilingan 160 mg yoki kuniga bir marta og'iz orqali qabul qilingan 320 mg.
View full prescribing information for Brukinsa.
