Comparative efficacy of ibrutinib versus other covalent Bruton tyrosine kinase inhibitors (cBTKis) in first-line (1L) chronic lymphocytic leukemia (CLL): A matched-adjusted indirect comparison (MAIC).

Danilov, A.V.; Shadman, M.; Burger, J.A.; Kittai, A.; O'Brien, S.M.; Tam, C.S.L.; Schulz, M.; Krigsfeld, G.; Huang, H.-H.; Stephens, D.M.; Munir, T.

Comparative efficacy of ibrutinib versus other covalent Bruton tyrosine kinase inhibitors (cBTKis) in first-line (1L) chronic lymphocytic leukemia (CLL): A matched-adjusted indirect comparison (MAIC).

All Authors

Danilov, A.V.

Shadman, M.

Burger, J.A.

Kittai, A.

O'Brien, S.M.

Tam, C.S.L.

Schulz, M.

Krigsfeld, G.

Huang, H.-H.

Stephens, D.M.

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LTHT Author

Munir, Talha

LTHT Department

Oncology
Haematology

Publication Date

2025

Item Type

Conference Abstract

Abstract

e19023Background: Ibrutinib (ibr), acalabrutinib (acala), and zanubrutinib (zanu) are cBTKis approved for treatment of CLL, with demonstrated efficacy as a single-agent in 1L CLL treatment. Existing data comparing treatment outcomes across cBTKis in 1L settings are limited. We conducted a MAIC analysis to compare efficacy outcomes of 1L treatment with ibr, acala, and zanu using data from the phase 3 RESONATE-2 (NCT01722487; NCT01724346), ELEVATE-TN (NCT02475681), and SEQUOIA (NCT03336333) trials, respectively. Method(s): Individual patient (pt) data from pts treated with ibr in RESONATE-2 were matched to aggregate baseline characteristic data from pts treated with acala and zanu in the ELEVATE-TN and SEQUOIA trials, respectively, using the method of MAIC. Baseline characteristics used for matching were age, sex, Eastern Cooperative Oncology Group performance status, Rai stage (III/IV), bulky disease (>=5 cm), presence of del(11q), beta2 microglobulin (>3.5 mg/L), and presence of TP53 mutation. Pts with missing baseline characteristic data were omitted. Safety outcomes were not assessed in this analysis and were published separately. After matching, adjusted progression-free survival (PFS) and overall survival (OS) for pts treated with ibr from RESONATE-2 (up to 10-y follow-up) were compared with corresponding outcomes from acala- and zanu-treated pts from ELEVATE-TN (overall median follow-up: 77.2 mo) and SEQUOIA cohort 1 (overall median follow-up: 62.0 mo). PFS and OS for acala and zanu were estimated using data extracted from published Kaplan-Meier curves. Result(s): The analysis included 537 pts treated with ibr (n=117), acala (n=179), or zanu (n=241). After matching, the effective sample sizes for ibr were reduced to 88 (vs acala) and 76 (vs zanu). PFS and OS rates were similar between weighted ibr and acala cohorts in the 1L setting; at the 74.5-mo follow-up, PFS (95% CI) rates were 69.5% (59.9-80.8%) and 60.8% (53.6-69.0%), respectively; OS (95% CI) rates were 83.4% (75.6-92.1%) and 74.0% (67.5-81.1%). A comparable trend was observed between weighted ibr and zanu cohorts, where at 60 mo, PFS rates were 76.1% (66.7-86.9%) and 75.7% (69.9-82.0%), and OS rates were 87.3% (79.8-95.4%) and 85.7% (81.2-90.3%), respectively. Median PFS and OS were not reached with ibr, acala, or zanu. Conclusion(s): This is the first MAIC analysis to compare long-term efficacy outcomes across cBTKis in the 1L treatment of CLL. In the absence of head-to-head 1L CLL trials, our results suggest that ibr provides similar efficacy outcomes to acala and zanu. Further analyses are needed to understand if cBTKis provide similar or different efficacy in specific pt populations, such as those with high-risk disease.