Real-world data showed zanubrutinib was associated with longer time to treatment discontinuation and higher persistence vs acalabrutinib or ibrutinib in first-line CLL.
First-line zanubrutinib (Brukinsa) was associated with a significantly lower risk of treatment discontinuation than those treated with acalabrutinib (Calquence) or ibrutinib (Imbruvica), according to real-world data presented in a poster session at the
In the retrospective analysis of 1850 patients, the adjusted risk of treatment discontinuation was 24% lower with zanubrutinib (n = 608) than with acalabrutinib (n = 826; adjusted HR, 0.76; 95% CI, 0.59-0.97; P = .0257) and 49% lower than with ibrutinib (n = 416; adjusted HR, 0.51; 95% CI, 0.39-0.66; P < .0001).
At 12 months, treatment persistence was highest with zanubrutinib at 82.8% (95% CI, 79.1%-85.9%), followed by acalabrutinib at 78.7% (95% CI, 75.4%-81.7%) and ibrutinib at 68.1% (95% CI, 62.8%-72.9%; P < .0001). At 24 months, rates of treatment persistence were 74.7% (95% CI, 69.3%-79.3%) with zanubrutinib, 66.3% (95% CI, 61.6%-70.6%) with acalabrutinib, and 58.7% (95% CI, 52.7%-64.3%) with ibrutinib (P = .0002).
“While this study provides comparative insights into real-world treatment discontinuation, additional studies with longer follow-up are needed to better understand the reasons for, and consequences of, treatment discontinuation in first-line CLL,” lead study author Nakhle Saba, MD, of Our Lady of the Lake Cancer Institute in Baton Rouge, Louisiana, and colleagues wrote in a poster.
Although past real-world studies have helped shed light on key efficacy outcomes for first-line BTK inhibitors in patients with CLL, including the older population, investigators of this retrospective study sought to better understand treatment patterns in clinical practice for these agents.1-3
Investigators leveraged the US IQVIA PharMetrics closed claims database to identify adult patients with at least 2 entries of International Classification of Diseases codes for CLL or small lymphocytic lymphoma who initiated first-line covalent BTK inhibitor monotherapy with ibrutinib, acalabrutinib, or zanubrutinib between January 1, 2022, and February 28, 2025.1 The index date was the date of first-line treatment initiation, and eligible patients had continuous health insurance enrollment for at least 3 months prior. Patients who received a BTK inhibitor as part of a clinical trial were excluded.
Treatment discontinuation was defined as the time from the index date to the regimen end date when followed by a subsequent therapy, or a gap of at least 120 days between the regimen end date and the last activity or enrollment date. Real-world time-to-treatment discontinuation was analyzed using Kaplan-Meier estimates, and a multivariable Cox proportional hazards model was adjusted for age, sex, race, ethnicity, payer type, geographic region, and Charlson Comorbidity Index.
The median follow-up was 12 months (IQR, 6-19) for zanubrutinib, 14 months (IQR, 7-25) for acalabrutinib, and 17 months (IQR, 8-28) for ibrutinib. Baseline characteristics were generally comparable, although the median age was higher with zanubrutinib than with acalabrutinib or ibrutinib (69.0 vs 68.0 vs 67.0 years; P = .0007), and a greater proportion of zanubrutinib-treated patients were 65 years of age or older (73.9% vs 68.9% vs 65.9%).
Investigators conducted a prespecified subgroup analysis in patients 65 years of age or older, with data mirroring the overall population outcomes.
At 12 months, treatment persistence rates were 82.7% (95% CI, 78.3%-86.3%) with zanubrutinib (n = 449), 78.0% (95% CI, 73.8%-81.6%) with acalabrutinib (n = 569), and 65.1% (95% CI, 58.3%-71.1%) with ibrutinib (n = 274; P < .0001). At 24 months, the respective rates were 73.6% (95% CI, 66.7%-79.3%), 65.6% (95% CI, 59.8%-70.8%), and 56.0% (95% CI, 48.4%-63.0%; P = .0018).
In the older subgroup, the adjusted risk of treatment discontinuation remained significantly lower with zanubrutinib vs acalabrutinib (adjusted HR, 0.74; 95% CI, 0.55-0.98; P = .0364) and ibrutinib (adjusted HR, 0.48; 95% CI, 0.36-0.66; P < .0001).
