Nov 2021: Asciminib (Scemblix, Novartis AG) dibéré persetujuan gancangan ku Administrasi Pangan sareng Narkoba pikeun penderita leukemia myeloid kronis kromosom-positip Philadelphia (Ph + CML) dina fase kronis (CP) anu saacanna nampi dua atanapi langkung sambetan tirosin kinase (TKI), ogé pikeun pasien dewasa. kalawan Ph + CML di CP anu miboga mutasi T315I.
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 keur diuji di penderita Ph + CML di CP jeung mutasi T315I di CABL001X2101 (NCT02081378), hiji multi-puseur, open-labél panalungtikan klinis. Éféktivitas asciminib 200 mg dua kali sadinten dina 45 pasien kalayan mutasi T315I ditaliti. Pasén tetep dina perlakuan dugi aranjeunna ngalaman karacunan teu kaampeuh atawa gagalna perlakuan. MMR mangrupikeun ukuran hasil éféktivitas primér. MMR kahontal dina 42 persén (19/45, interval kapercayaan 95 persén: 28 persén nepi ka 58 persén) pasien sanggeus 24 minggu. MMR kahontal dina 49 persén pasien (22/45, 95 persén interval kapercayaan: 34 persén nepi ka 64 persén) sanggeus 96 minggu. Rata-rata waktos perlakuan nyaéta 108 minggu (rentang, 2 dugi ka 215 minggu).
Inféksi saluran pernapasan luhur, nyeri muskuloskeletal, kacapean, seueul, ruam, sareng diare mangrupikeun efek samping anu paling umum (20%). Turunna jumlah trombosit, ningkat trigliserida, turunna jumlah neutrofil sareng hémoglobin, sareng paningkatan kréatin kinase, alanin aminotransferase, lipase, sareng amilase mangrupikeun abnormalitas laboratorium anu paling umum.
Dina pasien kalayan Ph + CML dina CP anu saacanna parantos dirawat ku dua atanapi langkung TKI, dosis asciminib anu disarankeun nyaéta 80 mg dikaluarkeun sacara lisan sakali dina waktos anu sami unggal dinten atanapi 40 mg dua kali sadinten dina interval 12 jam. Dina pasien kalayan Ph + CML dina CP kalayan mutasi T315I, dosis asciminib anu disarankeun nyaéta 200 mg dua kali sapoé dina interval kira-kira 12 jam.
