Real-world comparative effectiveness of covalent Bruton tyrosine kinase inhibitors (cBTKi) among
patients with relapsed/refractory mantle cell lymphoma (R/R MCL)
Authors: Tycel Phillips1, Taavy A. Miller2, Jingru Wang2, Mark A. Guinter2, Amy Pierre2, Gregory A.
Maglinte3, Erlene K. Seymour3
Affiliations: 1City of Hope, Duarte, California, United States of America, 2Flatiron, New York, UnitedStates of America, 3BeiGene USA, Inc., San Mateo, CA, United States of America
ABSTRACT
Objectives: Treatment for R/R MCL has evolved with the use of cBTKi monotherapy, yet little is known
about their relative effectiveness or utilization across patient (pt) groups based on race or biomarker
status in the real-world (RW) setting. This study aimed to describe characteristics and utilization
patterns and compare the RW effectiveness of zanubrutinib (zanu) with acalabrutinib (acala) andibrutinib (ibru) monotherapy.
Methods: This retrospective cohort study included adult pts diagnosed with R/R MCL who initiated firsttreatment with a cBTKi in the second line (2L) or third line (3L) on 01/01/2018, or later, and were
followed until death or loss to follow-up using the US nationwide Flatiron Health electronic healthrecord derived deidentified database. Patient characteristics and survival estimates based on KaplanMeier (KM) analyses were summarized with descriptive statistics; inverse probability of treatment
weighting (IPTW) and multivariable adjustment were used in adjusted Cox models to compare RW timeto-next treatment (rwTTNT) and overall survival (rwOS).
Results: Of the 1377 R/R MCL pts who received 2L+ lines of therapy, 602 had received cBTKimonotherapy in 2L or 3L for MCL and were included in this study. Median age was 74 (range, 34-85 yrs),
majority of pts were male (74%), White (White 76%, Black 3.5%, Asian 1.5%, Other race 8%, Unknown11%), and non-Hispanic/Latino (non-Hispanic/Latino 75%, Hispanic/Latino 5.6%, Unknown 19%).
Patients varied by socioeconomic status (SES; from low to high SES index 1 [12%], 2 [16%], 3 [20%], 4[24%], 5 [19%], Unknown [10%]). Patients also varied by baseline ECOG performance status, Ki67, andLDH. Most pts had stage III/IV at diagnosis (74%). Only 26 (4.3%) pts had a positive documented TP53
status at 2L/3L index. Among pts who received their first cBTKi at 2L or 3L index therapy, 107 received
zanu (2L [79%], 3L [21%]), 301 received acala (2L [80%], 3L [20%]), and 194 received ibru (2L [84%], 3L[16%]). Follow-up times (median [IQR]) from start of 2L for each cBTKi were zanu 17 mo (9, 31), acala 35
mo (20, 51), and ibru 53 mo (35, 62). Among the overall 2L/3L cBTKi monotherapy cohort, medianrwTTNT was 11.1 mo (95% CI: 9.2, 12.9) and median rwOS was 29.2 mo (95% CI: 24.3, 36.5). The medianrwTTNT for zanu was 16.8 mo (95% CI: 11.8, 23.7), acala 11.5 mo (95% CI: 8.6, 14.6), and ibru 8.6 mo(95% CI: 7.2, 11.3); P=0.06. The median rwOS was not reached (NR) for zanu (95% CI: 23.7, NR), acala27.4 mo (95% CI: 22.7, 36.5), and ibru 29.3 mo (95% CI: 21.1, 40.5); P=0.12. The rwTTNT and rwOS
trends persisted when comparing each cBTKi at 3, 6, 9, and 12 mo (Table). Adjusted, multivariable
models showed significantly longer rwTTNT (HR: 0.68 [95% CI: 0.49, 0.94]; P=0.02) and rwOS (HR: 0.64
[95% CI: 0.41, 0.99]; P=0.04) for zanu when compared to ibru, and longer but non-significant trends in
rwTTNT (HR: 0.82 [95% CI: 0.59, 1.12]; P=0.20) and rwOS (HR: 0.69 [95% CI: 0.46, 1.06]; P=0.09) for zanu
compared to acala.
Conclusions: Among RW pts with R/R MCL who received cBTKi monotherapy, zanu had a significantly
longer rwTTNT and rwOS compared to ibru, and a trend favoring zanu was observed in rwTTNT andPPLC 2024

rwOS when compared to acala. Limited sample size and follow-up with zanu restricted the ability todiscern smaller differences in effectiveness as compared to the other cBTKi. Other limitations include
the retrospective nature of the study and limited sample size in subgroups. Given low utilization of cBTKi
monotherapy among Black, Indigenous, and people of color (BIPOC) pts and potentially low testing of
TP53, further investigation into RW R/R MCL treatment patterns and outcomes by race/ethnicity andbiomarker status is warranted.

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