First-line zanubrutinib (Brukinsa) monotherapy was associated with improved real-world efficacy compared with ibrutinib (Imbruvica) or acalabrutinib (Calquence) in older patients with chronic lymphocytic leukemia (CLL), according to data from a retrospective analysis using Medicare data, which was presented at the
In adjusted Cox models, patients with CLL who were Medicare beneficiaries and received zanubrutinib (n = 3006) experienced a median time to treatment discontinuation (TTD) that was not reached (NR; 95% CI, NR-NR) compared with 24 months (95% CI, 22-25) for those who received acalabrutinib (n = 4309) and 14 months (95% CI, 13-15) for those who received ibrutinib (n = 3208).
The median time to next treatment (TTNT) for patients who received zanubrutinib was NR (95% CI, 45-NR) vs 40 months (95% CI, 38-42) for acalabrutinib and 30 months (95% CI, 29-32) for ibrutinib. Moreover, the median overall survival (OS) was NR across all groups in the analysis.
Notably, median follow-up for the zanubrutinib group was 15.8 months (range, 0.1-61.2), 20.7 months (range, 0-69.2) for acalabrutinib, and 34.9 monhts (range, 0-69.4) for ibrutinib.
“In this large, real-world cohort of patients who were at least 65 years [of age] with the longest follow-up to date, zanubrutinib monotherapy was associated with significantly better TTD, TTNT, and OS compared with ibrutinib and acalabrutinib,” Daniel A. Ermann, MD, and coauthors wrote in a poster of the data.
Ermann is an associate professor in the Division of Hematology and Hemotologic Malignancies and physician lead of the CLL Trials Program at Huntsman Cancer Institute in Salt Lake City, Utah.
Interested in seeing more data on real-world BTK inhibitors like zanubrutinib and acalabrutinib? Be sure to check out a post hoc
Prior real-world analyses were frequently limited by short follow-up, small sample sizes, or single-institution cohorts, Ermann and colleagues noted. To address the first-line gap in an older population, investigators used the de-identified Medicare Fee-for-Service database to compare clinical outcomes across the 3 FDA-approved BTK inhibitors.
The retrospective, observational cohort study identified patients with CLL or small lymphocytic lymphoma who started first-line BTK inhibitor monotherapy with ibrutinib, acalabrutinib, or zanubrutinib between January 1, 2020, and September 30, 2025, with a 12-month baseline period before the index date.
Outcomes of rwTTD, rwTTNT, and rwOS were assessed from the start of first-line treatment. Discontinuation was defined as a subsequent systemic therapy after the current line, a gap of more than 180 days with no systemic therapy after the last drug episode, or date of death.
Median time to event and landmark probabilities at 12 and 24 months were estimated with Kaplan-Meier methods, and adjusted hazard ratios were derived from Cox proportional hazards models controlling for age, sex, race and ethnicity, Charlson Comorbidity Index, and year of first-line initiation. A stratified analysis was performed by age group (65-74, 75-84, and ≥85 years).
Baseline characteristics among all patients (n = 10,523) revealed that patients were mostly 75 to 79 years of age (23.7%) or 70 to 74 years old (24.1%). Most patients were male (58.3%), non-Hispanic White (89.3%), and resided in urban areas (78.0%). Hypertension was reported in 64.7% of patients, and atrial fibrillation was reported in 17.1%, 17.2%, and 11.6% of patients treated with zanubrutinib, acalabrutinib, and ibrutinib, respectively.
Median age at first-line initiation was 77 years for zanubrutinib (interquartile range [IQR], 72-82) and acalabrutinib (IQR, 72-83), and 76 years (IQR, 71-82) for ibrutinib.
The 12- and 24-month TTD rates for the zanubrutinib group were 72.3% (95% CI, 70.5%-73.9%) and 63.2% (95% CI, 61%-65.4%), respectively. These respective rates were 62.6% (95% CI, 61%-64.1%) and 48.9% (95% CI, 47.1%-50.6%) for acalabrutinib (HR vs zanubrutinib, 0.86; 95% CI, 0.78-0.94; P = .0007); and 52.9% (95% CI, 51.1%-54.7%) and 35.1% (95% CI, 33.4%-36.9%) for Ibrutinib (HR vs zanubrutinib, 0.57; 95% CI, 0.51-0.64; P < .0001).
Additionally, 12- and 24-month TTNT rates for zanubrutinib were 82.3% (95% CI, 80.8%-83.7%) and 71.3% (95% CI, 69.1%-73.4%), respectively. These respective rates were 78.4% (95% CI, 77%-79.6%) and 66.7% (95% CI,79.6%) for acalabrutinib (HR vs zanubrutinib, 0.87; 95% CI, 0.78-0.96; P =.008); and 73.8% (95% CI, 72.2%-75.3%) and 56.4% (95%CI, 54.6%-58.1%) for ibrutinib (HR vs zanbrutinib, 0.63; 95% CI, 0.55-0.71; P <.0001).
OS rates at 12 and 24 months were 90.8% (95% CI, 89.7%-91.9%) and 85.9% (95% CI, 84.2%-87.4%), respectively, with zanubrutinib. These respective rates were 86.9% (95% CI, 85.8%-87.9%) and 79.7% (95% CI, 78.3%-81%) with acalabrutinib (HR vs zanubrutinib, 0.76; 95% CI, 0.66-0.88; P =.0002); and 84.8%(95% CI, 83.5%-86%) and 75.4% (95%Ci, 73.8%-76.9%) with ibrutinib (HR vs zanubrutinib, 0.64; 95% CI, 0.54-0.77; P <.0001).
Zanubrutinib was associated with statistically significantly longer TTD and TTNT than ibrutinib across all age groups, and longer TTD and TTNT than acalabrutinib in the 65-to-74-year and 75-to-84-year subgroups. When compared with ibrutinib, zanubrutinib was associated with a 33% to 44% lower risk of death across age groups (ages 65-74, HR, 0.56; 95% CI, 0.36-0.86; P = .008; ages 75-84; HR, 0.66 95% CI, 0.50-0.87; P =. 003; ages ≥85; HR, 0.67; 95% CI, 0.51-0.88; P = .004).
When compared with acalabrutinib, zanubrutinib was associated with a 45% lower risk of death in patients 65 to 74 years of age (HR, 0.55; 95% CI, 0.38-0.81; P = .002) and a 27% lower risk in those 75 to 84 years of age (HR, 0.73; 95% CI, 0.59-0.91; P = .005). However, differences in OS rates were not statistically significant in patients at least 85 years of age (HR, 0.91; 95% CI, 0.73-1.1; P = .35).
Disclosures: Ermann reported honoraria from BeOne Medicines; a consulting or advisory role with BeOne Medicines and ADC Therapeutics; and a speakers bureau role with Incyte and AstraZeneca. The study was sponsored by BeOne Medicines, and several coauthors reported employment with the company.
