Zanubrutinib receives FDA approval for patients with CLL or SLL

January 2023 Pharma News Nalinee Pathak
Diffuse Large B-Cell Lymphoma (DLBCL) of Stomach is a rare, B-cell non-Hodgkin’s lymphoma that affects older adults. It is a subtype of lymphoma of stomach that is more aggressive and rapid-growing than other subtypes. In majority of cases, the lymphoma is a type of primary non-Hodgkin lymphoma. This means that it first involves the stomach and later can involve other parts of the body including the lymph nodes and bone marrow.

The Food and Drug Administration (FDA) has approved zanubrutinib, a selective Bruton tyrosine kinase (BTK) inhibitor, for patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL).  The regulatory approval was granted based on the results of the pivotal SEQUOIA and ALPINE trials.

The B-cell receptor (BCR) signalling pathway plays an important role in the pathogenesis of many B-cell malignancies, including CLL/SLL. BTK forms a key component of the BCR pathway, making it an attractive therapeutic target in patients with CLL or SLL. Zanubrutinib is a selective, next-generation BTK inhibitor whose efficacy in the treatment of CLL/SLL was evaluated in two randomised trials.


The randomised SEQUOIA trial included patients with treatment naïve CLL or SLL and randomly assigned them to receive either zanubrutinib (until disease progression or unacceptable toxicity) or bendamustine plus rituximab (BR). The study’s primary outcome was progression-free survival (PFS) as assessed by an independent review committee. In the cohort of patients without a 17p deletion (n=479), a significantly longer PFS was seen with zanubrutinib compared to BR (median not reached    vs 33.7 months; HR = 0.42; 95% CI, 0.28-0.63). The overall response rate (ORR) was superior (94.6%) in the zanubrutinib arm than the BR arm (85.3%). Additionally, in the cohort (n=110) with 17p deletion, the 24-month PFS rate was 88.9%, and the ORR of 88% was observed with zanubrutinib treatment.


The ALPINE study enrolled 652 patients with relapsed or refractory CLL or SLL and randomised them to either zanubrutinib or ibrutinib. A superior ORR of 80% was seen with zanubrutinib as compared to ibrutinib (73%). The investigator-assessed rates of PFS were also higher in the zanubrutinib group (78.4%) than in the ibruitinib arm (65.9%).

Overall, zanubrutinib proved to be tolerable across both trials. The most common adverse events associated with this agent across both trials were a decreased neutrophil count (42%), upper respiratory tract infections (39%), a decreased platelet count (34%), haemorrhage (30%) and musculoskeletal pain (30%). Secondary malignancies were seen in 13% of patients, atrial fibrillation in 3.7% and grade 3 or higher ventricular arrhythmias in 0.2% of patients.

Based on the clinical efficacy of zanubrutinib in two clinical trials, the FDA has approved its use for treating patients with CLL or SLL.


FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma.