Veljače 2023 .: FDA je odobrila zanubrutinib (Brukinsa, BeiGene USA, Inc.) za kroničnu limfocitnu leukemiju (CLL) ili mali limfocitni limfom (SLL).
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 je procijenio učinkovitost u bolesnika s relapsom ili refraktornim CLL/SLL (NCT03734016). Ukupno 652 sudionika nasumično su dodijeljena ili zanubrutinibu ili ibrutinibu. 1 je bio srednji broj prethodnih linija liječenja (raspon 1-8). ORR i DOR bile su primarne mjere ishoda učinkovitosti u ovom trenutku analize odgovora, prema IRC-u. ORR za skupinu koja je primala zanubrutinib bio je 80% (95% CI: 76, 85), a za skupinu koja je primala ibrutinib bio je 73% (95% CI: 68, 78) (omjer stope odgovora: 1.10, 95% CI: 1.01, 1.20; p=0.0264). Nakon medijana praćenja od 14.1 mjesec, niti jedna ruka nije dosegla medijan DOR.
Najčešće nuspojave zanubrutiniba (30%) uključivale su krvarenje (42%), infekciju donjeg dišnog sustava (39%), smanjen broj trombocita (34%), smanjen broj neutrofila (42%) i mišićno-koštanu bol (30%). . U 13% pojedinaca pojavile su se sekundarne primarne zloćudne bolesti, kao što su ne-kožni karcinomi. 3.7% bolesnika imalo je fibrilaciju ili lepršanje atrija, dok je 0.2% bolesnika imalo ventrikularne aritmije stupnja 3 ili više.
Dok bolest ne napreduje ili dok ne dođe do nepodnošljive toksičnosti, preporučena doza zanubrutiniba je 160 mg oralno dva puta dnevno ili 320 mg oralno jednom dnevno.
View full prescribing information for Brukinsa.
