Real-World Comparative Effectiveness of Bruton Tyrosine Kinase Inhibitors in Relapsed/Refractory Mantle Cell Lymphoma Open Access

• Zanubrutinib had significantly longer rwOS vs. ibrutinib and trends for improved rwTTNT vs. ibrutinib and rwTTNT/rwOS vs. acalabrutinib.

• Toxicity was a frequently documented reason for patients who changed to another cBTKi monotherapy.

This real-world retrospective cohort study evaluated utilization and comparative effectiveness of covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapies in relapsed/refractory mantle cell lymphoma (R/R MCL) from electronic health records in the United States. Adults with R/R MCL who received second- or third-line (2L/3L) zanubrutinib, acalabrutinib, or ibrutinib monotherapy, on or after January 1, 2018, were included. Inverse probability of treatment weighting was used in adjusted Cox models to compare real-world time-to-next treatment (rwTTNT) and overall survival (rwOS). Among 698 patients who received 2L/3L cBTKi monotherapy, 49%, 32%, and 19% received acalabrutinib, ibrutinib, and zanubrutinib, respectively. Unadjusted analyses showed median rwTTNT for 2L zanubrutinib, acalabrutinib, and ibrutinib was 14.5 (95%CI 11.0-23.2), 12.8 (95%CI 10.5-15.6), and 10.3 (95%CI 7.6-13.7) months and median rwOS was 26.4 (95%CI 23.2-not reached [NR]), 29.2 (95%CI 22.9-38.1), and 29.3 (95%CI 21.8-41.6) months, respectively. Median rwTTNT for 3L zanubrutinib, acalabrutinib, and ibrutinib was 21.1 (95%CI 3.9-NR), 9.2 (95%CI 6.8-14.7), and 9.6 (95%CI 4.8-18.0) months and median rwOS was NR (95%CI 27.3-NR), 27.4 (95%CI 15.1-42.2), and 27.0 (95%CI 15.6-NR) months, respectively. Adjusted models in the 2L/3L cohorts combined showed numerically longer rwTTNT and statistically significantly longer rwOS for zanubrutinib versus ibrutinib (hazard ratio 0.63, 95%CI 0.42-0.96), and trends for improved rwTTNT and rwOS for zanubrutinib over acalabrutinib. Toxicity was a frequent reason for changing to another cBTKi. These findings suggest potential improvements in rwTTNT and rwOS with the use of second- and next-generation cBTKis for R/R MCL from 2018 and beyond.