2023. feb: Zanubrutinib (Brukinsa, BeiGene USA, Inc.) er godkendt af FDA til kronisk lymfatisk leukæmi (CLL) eller lille lymfatisk lymfom (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 vurderede effektiviteten hos patienter med recidiverende eller refraktær CLL/SLL (NCT03734016). 652 deltagere i alt blev tilfældigt tildelt enten zanubrutinib eller ibrutinib. 1 var mediantallet for tidligere behandlingslinjer (interval 1-8). ORR og DOR var de primære effektmål på dette tidspunkt i responsanalysen ifølge en IRC. ORR for zanubrutinib-armen var 80 % (95 % CI: 76, 85) og for ibrutinib-armen var 73 % (95 % CI: 68, 78) (responsratio: 1.10, 95 % CI: 1.01, 1.20; p=0.0264). Efter en median opfølgning på 14.1 måneder havde ingen af armene nået median DOR.
De hyppigste bivirkninger af zanubrutinib (30 %) omfattede blødning (42 %), nedre luftvejsinfektion (39 %), nedsat antal blodplader (34 %), nedsat antal neutrofiler (42 %) og muskel- og skeletsmerter (30 %) . Hos 13 % af individerne forekom sekundære primære maligniteter, såsom ikke-hudkarcinomer. 3.7 % af patienterne havde atrieflimren eller flagren, mens 0.2 % af patienterne havde ventrikulære arytmier grad 3 eller derover.
Indtil sygdommen skrider frem, eller der er utålelig toksicitet, er den anbefalede zanubrutinib-dosis 160 mg oralt to gange dagligt eller 320 mg oralt én gang dagligt.
View full prescribing information for Brukinsa.
