Nov 2021: Asciminib (Scemblix, Novartis AG) inikezwe ukugunyazwa okusheshisiwe yi-Food and Drug Administration yeziguli ezine-Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) ezisesigabeni esingamahlalakhona (CP) ngaphambili ezazithole ama-tyrosine kinase inhibitors (TKIs) amabili noma ngaphezulu, kanye neziguli zabantu abadala. nge-Ph+ CML ku-CP enokuguqulwa kwe-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.
I-Asciminib ihlolwa ezigulini ezine-Ph+ CML ku-CP ngokuguqulwa kwe-T315I ku-CABL001X2101 (NCT02081378), uphenyo lomtholampilo olunamaphakathi amaningi, olunamalebula avulekile. Ukusebenza kwe-asciminib 200 mg kabili ngosuku ezigulini ezingama-45 ezinokuguqulwa kwe-T315I kwacwaningwa. Iziguli zazigcinwa ngokwelashwa kuze kube yilapho zithola ubuthi obungabekezeleleki noma ukwehluleka kokwelashwa. I-MMR yayiyisilinganiso esiyinhloko somphumela wokusebenza ngempumelelo. I-MMR ifinyelelwe ngamaphesenti angu-42 (19/45, isikhathi sokuzethemba samaphesenti angu-95: amaphesenti angu-28 kuya kumaphesenti angu-58) ezigulini ngemva kwamasonto angu-24. I-MMR ifinyelelwe kumaphesenti angu-49 eziguli (22/45, isikhathi sokuzethemba esingamaphesenti angu-95: amaphesenti angu-34 kuya kumaphesenti angu-64) ngemva kwamasonto angu-96. Isikhathi sokwelashwa esijwayelekile sasingamaviki ayi-108 (ububanzi, amaviki ama-2 kuye kwangama-215).
Izifo zepheshana lokuphefumula eliphezulu, ubuhlungu be-musculoskeletal, ukukhathala, isicanucanu, ukuqubuka, kanye nesifo sohudo yimiphumela emibi evame kakhulu (20%). Ukwehla kwezibalo zamaplatelet, ukwanda kwe-triglycerides, ukwehla kwezibalo ze-neutrophil ne-hemoglobin, kanye nokwenyuka kwe-creatine kinase, i-alanine aminotransferase, i-lipase, ne-amylase yizinto ezingavamile zaselabhorethri ezivame kakhulu.
Ezigulini ezine-Ph+ CML ku-CP ezike zelashwa ngaphambilini ngama-TKI amabili noma ngaphezulu, umthamo onconyiwe we-asciminib ngu-80 mg ophathwa ngomlomo kanye ngosuku ngesikhathi esifanayo nsuku zonke noma u-40 mg kabili ngosuku cishe ngezikhathi zamahora ayi-12. Ezigulini ezine-Ph+ CML ku-CP enokuguqulwa kwe-T315I, umthamo ophakanyisiwe we-asciminib ngu-200 mg kabili ngosuku cishe ngezikhathi zamahora angu-12.
