The findings, coming from the phase 3 SEQUOIA study, found that the next-generation, selective Bruton tyrosine kinase inhibitor had superior efficacy versus chemoimmunotherapy and demonstrated an acceptable safety profile among 600 older patients with comorbidities.
Zanubrutinib may be a new potential frontline treatment option for patients with untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), including among a subgroup of hard-to-treat patients, according to recent research.
The findings, coming from the phase 3 SEQUOIA study, found that the next-generation, selective Bruton tyrosine kinase inhibitor had superior efficacy versus chemoimmunotherapy and demonstrated an acceptable safety profile among 600 older patients with comorbidities.
“SEQUOIA is, to our knowledge, the first randomised, phase 3 study examining the efficacy and safety of zanubrutinib in patients with untreated CLL,” explained the researchers, adding, “The SEQUOIA study provides aggregate data supporting the potential use of zanubrutinib as a new treatment option for patients with untreated CLL or SLL.”
Compared with bendamustine-rituximab, zanubrutinib significantly improved progression-free survival (PFS) (HR, 0.42; 95% CI, 0.28-0.63) among patients without the high-risk genetic abnormality del(17)(p13.1), meeting the primary endpoint of the study.
At a median follow-up of 26.2 months, median PFS was not reached among either group. Estimated PFS at 24 months was 85% among patients receiving zanubrutinib and was 69.5% among patients receiving bendamustine-rituximab. According to the researchers, their findings are consistent with previous randomized trials, including of ibrutinib (Alliance A041202) and of acalabrutinib (ELEVATETN), among patients with comorbidities.
Patients receiving zanubrutinib also experienced a higher overall response rate (94.6% vs 85.3%) as determined by an independent review committee. The researchers noted that BTK inhibitors are uncommon within the first 3 years of treatment, resulting in a need for longer follow-up to determine if responses to zanubrutunib deepen over time.
The study also included a group of patients with del(17)(p13.1)—a group of patients who historically have poor outcomes with chemoimmunotherapy—who were treated with zanubrutinib and at 24 months had an estimated PFS of 88.9%.
Patients receiving zanubrutinib received the treatment orally twice a day at 160 mg for 28-day cycles and patients receiving bendamustine-rituximab received bendamustine at 90 mg/m2 of body surface area on days 1 and 2 for 6 cycles plus rituximab at 375 mg/m2 of body surface area the day before or on day 1 of cycle 1, and 500 mg/m2 of body surface area on day 1 of cycles 2–6.
Across all 3 groups of patients, the most common grade 3 or worse adverse event was neutropenia, occurring in 11% of patients without del(17)(p13.1) receiving zanubrutinib, 51% of patients without del(17)(p13.1) receiving bendamustine-rituximab, and in 15% of patients with del(17)(p13.1) receiving zanubrutinib.
“Consistent with the known class effects of BTK inhibitors, bleeding adverse events occurred more often in patients treated with zanubrutinib. Several patients who reported major bleeding adverse events were concurrently administered antithrombotic medications, which might have contributed to these events,” wrote the researchers. “Overall, rates of anygrade bleeding events were similar to those reported in studies of other BTK inhibitors. Alliance A041202 and ELEVATETN required stopping of anticoagulation before enrolment, whereas our study did not restrict anticoagulation use at study entry; differences in study conduct might confound comparison of bleeding rates between BTK inhibitors.”
Among patients with del(17)(p13.1), rates of infection were similar between both treatment groups. Patients receiving zanubrutinib were more likely to report worse COVID-19 infection than patients receiving bendamustine-rituximab. The group flagged limitations of the study brought on by the COVID-19 epidemic, including prevention of certain sites being able to complete all study assessments, including bone marrow examinations.
Reference
Tam C, Brown J, Kahl B, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. Published online July 7, 2022. doi: 10.1016/S1470-2045(22)00293-5
Surgery, Chemotherapy Considered Protective Survival Factors in Patients With OC, Liver Metastases
May 21st 2024Surgery and chemotherapy significantly improved both overall survival (OS) and cancer-specific survival (CSS) in patients with liver metastases originating from ovarian cancer (OC), who generally face a poor prognosis with a 5-year survival rate of less than 30%.
Read More
Frameworks for Advancing Health Equity: Urban Health Outreach
May 9th 2024In the series debut episode of "Frameworks for Advancing Health Equity," Mary Sligh, CRNP, and Chelsea Chappars, of Allegheny Health Network, explain how the Urban Health Outreach program aims to improve health equity for individuals experiencing homelessness.
Listen
Unique Case: HCC With No Cirrhosis—and “Hidden” CLL/SLL
May 21st 2024A 77-year-old man had no risk factors for hepatocellular carcinoma (HCC), but he was nonetheless found to have it. Along the way, he was also diagnosed with previously undetected chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Read More