2021 yil noyabr: Asciminib (Scemblix, Novartis AG) Oziq-ovqat va farmatsevtika idorasi tomonidan ilgari ikki yoki undan ortiq tirozin kinaz inhibitörlerini (TKI) olgan surunkali fazadagi (CP) Filadelfiya xromosomasi-musbat surunkali miyeloid leykemiya (Ph + CML) bilan og'rigan bemorlar, shuningdek kattalar bemorlari uchun tezlashtirilgan ruxsatnoma berildi. T315I mutatsiyasiga ega bo'lgan CPda Ph+ CML bilan.
ASCEMBL (NCT03106779) is a multi-center, randomised, active-controlled, open-label clinical trial investigating asciminib in patients with Ph+ CML in CP who have had two or more TKIs before. A total of 233 patients were randomly assigned (2:1) to receive either asciminib 40 mg twice daily or bosutinib 500 mg once daily, based on their significant cytogenetic response (MCyR) status. Patients were kept on treatment until they experienced intolerable toxicity or treatment failure. At 24 weeks, the main efficacy outcome measure was the major molecular response (MMR). The MMR rate in patients treated with asciminib was 25% (95 percent CI: 19, 33) compared to 13% (95 percent CI: 6.5, 23; p=0.029) in those treated with bosutinib. The median length of MMR has not yet been attained, with a median follow-up of 20 months.
Asciminib ko'p markazli, ochiq yorliqli klinik tadqiqot bo'lgan CABL315X001 (NCT2101) da T02081378I mutatsiyasiga ega bo'lgan CPda Ph+ CML bilan og'rigan bemorlarda sinovdan o'tkazilmoqda. T200I mutatsiyasiga ega 45 bemorda kuniga ikki marta 315 mg asciminibning samaradorligi o'rganildi. Bemorlar chidab bo'lmas toksiklikni boshdan kechirmaguncha yoki davolash samarasiz bo'lgunga qadar davolanishni davom ettirdilar. MMR asosiy samaradorlik ko'rsatkichi edi. MMR 42 haftadan so'ng bemorlarning 19 foizida (45/95, 28 foiz ishonch oralig'i: 58 foizdan 24 foizgacha) erishildi. MMR 49 haftadan so'ng bemorlarning 22 foizida (45/95, 34 foiz ishonch oralig'i: 64 foizdan 96 foizgacha) erishildi. O'rtacha davolanish muddati 108 hafta (diapazon, 2 dan 215 haftagacha).
Yuqori nafas yo'llarining infektsiyalari, mushak-skelet tizimining og'rig'i, charchoq, ko'ngil aynishi, toshma va diareya eng ko'p tarqalgan nojo'ya ta'sirlardir (20%). Trombotsitlar sonining kamayishi, triglitseridlarning ko'payishi, neytrofillar va gemoglobinning kamayishi, kreatin kinaz, alanin aminotransferaza, lipaza va amilaza ko'tarilishi eng keng tarqalgan laboratoriya anormalliklaridir.
Ilgari ikki yoki undan ortiq TKI bilan davolangan CPda Ph+ CML bo'lgan bemorlarda tavsiya etilgan asciminib dozasi kuniga bir marta og'iz orqali kuniga taxminan bir vaqtning o'zida 80 mg yoki taxminan 40 soatlik interval bilan kuniga ikki marta 12 mg ni tashkil qiladi. T315I mutatsiyasiga ega bo'lgan CPda Ph+ CML bo'lgan bemorlarda tavsiya etilgan asciminib dozasi taxminan 200 soatlik interval bilan kuniga ikki marta 12 mg ni tashkil qiladi.
