Real-world comparative effectiveness of covalent Bruton tyrosine kinase inhibitors (cBTKi) among
patients with relapsed/refractory mantle cell lymphoma (R/R MCL)
Tycel Phillips*1, Mark Guinter2, Taavy Miller2, Jingru Wang2, Amy Pierre2, Gregory A. Maglinte3, Erlene K.
Seymour3
1City of Hope, Duarte, California, United States of America, 2Flatiron, New York, United States of America,
3BeiGene USA, Inc., San Mateo, CA, United States of America

Background: 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.
Aims: The study aimed to describe characteristics and utilization patterns and compare RW
effectiveness of zanubrutinib (zanu) with acalabrutinib (acala) and ibrutinib (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 any 2L+ lines of therapy, 602 had received cBTKi
monotherapy in 2L or 3L for MCL and were included in this study. Median age was 74 (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), andibru 53 mo (35, 62).
Among the overall 2L/3L cBTKi monotherapy cohort, median rwTTNT was 11.1 mo (95% CI: 9.2, 12.9)
and median rwOS was 29.2 mo (95% CI: 24.3, 36.5). The median rwTTNT 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 medianrwOS was not reached (NR) for zanu (95% CI: 23.7, NR), acala 27.4 mo (95% CI: 22.7, 36.5), and ibru 29.3mo (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). All models (unadjusted not shown) showed significantly longer rwTTNT andEHA 2024

rwOS for zanu when compared to ibru, and longer but non-significant trends in rwTTNT and rwOS forzanu compared to acala.
Summary/Conclusions: Among RW pts with R/R MCL who received cBTKi monotherapy, zanu had asignificantly longer rwTTNT and rwOS compared to ibru, and a trend favoring zanu was observed inrwTTNT and rwOS when compared to acala. Limited sample size and follow-up with zanu restricted theability to discern 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 utilizationof 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 and biomarker status is warranted.

Table. Unadjusted and adjusted survival estimates of rwTTNT and rwOS comparing 2L/3L cBTKi
monotherapy (zanu, acala, ibru) among pts with R/R MCL
Unadjusted KM estimates of rwTTNT and rwOS and probability of continued treatment or survivalat 3, 6, 9, and 12 months
Median rwTTNT (95% CI)
3 months
6 months
9 months
12 months
Median rwOS (95% CI)
3 months
6 months
9 months
12 months

Overall, N=602
11.1 (9.2, 12.9)
80% (76%, 83%)
65% (62%, 69%)54% (50%, 59%)
47% (43%, 51%)29.2 (24.3, 36.5)
90% (88%, 93%)82% (79%, 85%)
74% (70%, 78%)70% (66%, 74%)

Zanu, N=107
16.8 (11.8, 23.7)
85% (78%, 92%)71% (62%, 80%)
65% (56%, 76%)58% (48%, 70%)
NR (23.7, NR)
96% (92%, 100%)89% (83%, 96%)84% (77%, 92%)
81% (72%, 90%)

Acala, N=301
11.5 (8.6, 14.6)
80% (75%, 85%)
65% (60%, 71%)
54% (49%, 60%)
48% (43%, 55%)
27.4 (22.7, 36.5)
90% (87%, 94%)81% (77%, 86%)
73% (68%, 79%)69% (64%, 75%)

Ibru, N=194
8.6 (7.2, 11.3)
77% (71%, 83%)
63% (56%, 70%)
49% (43%, 57%)40% (34%, 48%)29.3 (21.1, 40.5)
87% (82%, 92%)79% (74%, 85%)
71% (64%, 77%)66% (59%, 73%)

Multivariate and propensity score-adjusted hazard ratios for rwTTNT and rwOS comparing 2L/3L
zanu with acala and ibru, respectively (reference treatment = acala or ibru)
rwTTNT
GroupN Events
HR (95% CI)
P-value
Zanu vs acala
Multivariate
2560.82 (0.59, 1.12)
0.20
IPTW
895
0.81 (0.59, 1.11)
0.20
Zanu vs ibru
Multivariate
201
0.68 (0.49, 0.94)
0.02
IPTW
530
0.67 (0.48, 0.94)
0.02
rwOS
Zanu vs acala
Multivariate
171
0.69 (0.46, 1.06)
0.09
IPTW
622
0.69 (0.45, 1.05)
0.08
Zanu vs ibru
Multivariate
128
0.64 (0.41, 0.99)
0.04
IPTW
339
0.61 (0.40, 0.95)
0.03

EHA 2024