The Food and Drug Administration ( FDA ) has approved Brukinsa ( Zanubrutinib ) for chronic lymphocytic leukemia ( CLL ) or small lymphocytic lymphoma ( SLL ).
Efficacy in patients with treatment-naïve CLL/SLL was evaluated in SEQUOIA. In the randomized cohort including patients without 17p deletion, 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.
The main efficacy outcome measure was progression-free survival ( PFS ) as determined by an independent review committee ( IRC ).
The median PFS was not reached ( 95% CI: NE, NE ) in the Zanubrutinib arm and was 33.7 months ( 95% CI: 28.1, NE ) in the BR arm ( hazard ratio, HR= 0.42, 95% CI: 0.28, 0.63; p less than or equal to 0.0001 ). Estimated median follow-up for PFS was 25.0 months.
In a separate non-randomized cohort of SEQUOIA, Zanubrutinib was evaluated in 110 patients with previously untreated CLL/SLL with 17p deletion. Overall response rate ( ORR ) per Independent Review Committee ( IRC ) was 88% ( 95% CI: 81, 94 ).
The median duration of response ( DOR ) was not reached after a median follow-up of 25.1 months.
Efficacy in patients with relapsed or refractory CLL/SLL was evaluated in ALPINE. A total of 652 patients were randomized 1:1 to receive either Zanubrutinib or Ibrutinib. The median number of prior lines of therapy was 1 ( range 1-8 ). The main efficacy outcome measures at this time of response analysis were ORR and DOR as determined by an IRC.
The ORR was 80% ( 95% CI: 76, 85 ) in the Zanubrutinib arm and 73% ( 95% CI: 68, 78 ) in the Ibrutinib arm ( response rate ratio, RRR=1.10, 95% CI: 1.01, 1.20; p=0.0264 ).
The median DOR was not reached in either arm, after a median follow-up of 14.1 months.
Across clinical trials of Zanubrutinib, the most common adverse reactions ( 30% or more ) were neutrophil count decreased ( 42% ), upper respiratory tract infection ( 39% ), platelet count decreased ( 34% ), hemorrhage ( 30% ), and musculoskeletal pain ( 30% ).
Second primary malignancies, including non-skin carcinomas, developed in 13% of patients.
Atrial fibrillation or flutter were reported in 3.7% of patients, and grade 3 or higher ventricular arrhythmias in 0.2% of patients.
The recommended Zanubrutinib dosage is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity. ( Xagena2023 )
Source: FDA, 2023