Real-world Bruton tyrosine kinase inhibitor treatment patterns and outcomes among patients withchronic lymphocytic leukemia or small lymphocytic lymphoma in US community oncology practices
Authors: Jing-Zhou Hou1, Simon Blanc2, Gregory A. Maglinte3, Anupama Vasudevan2, Anna Rui2, MikeGart2, Hoa Pham3, Lindsay Aton2, Brandon Wang2, Rushir Choksi1
Affiliations: 1UPMC, Pittsburgh, Pennsylvania, United States of America, 2Integra Connect, West PalmBeach, Florida, United States of America, 3BeiGene USA, Inc., San Mateo, CA, United States of America
ABSTRACT
Objectives: Bruton tyrosine kinase inhibitor (BTKi) therapies are standard of care for chronic
lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), with acalabrutinib (acala) andzanubrutinib (zanu) having improved safety profiles vs ibrutinib (ibru). This study assessed real-world
clinical characteristics, treatment patterns, and adverse events (AEs) among BTKi-treated patients withCLL/SLL.
Methods: This is a retrospective observational study, updated with 5 months of additional data from aprevious analysis. Adults in the US community oncology setting initiated BTKi treatment between
January 1, 2020, and July 31, 2023, and were followed to October 31, 2023. De-identified structured
electronic health records were analyzed from the Integra Connect-PrecisionQ real-world database.
Cardiovascular (CV) AEs (based on ICD codes), time to treatment discontinuation (TTD), and time to next
treatment (TTNT) were reported.
Results: A total of 3064 patients initiated BTKi therapies during the index period (1L n=2815; 2L+ n=249).
Median age (range) was 72 years (33-90) in 1L and 72 years (42-89) in 2L+. There were 63.1% and 65.5%
males in 1L and 2L+, respectively. In 1L, 49.3% of patients were treated with ibru, 43.4% with acala, and7.2% with zanu. Similar trends were observed for 2L+. More patients experienced CV AEs among those
who received 1L ibru vs acala or zanu; 12.1%, 7.6%, and 7.3% at month 6 (P<0.05) and 14.6%, 9.4%, and8.5% at month 9 (P<0.05). Of patients treated with 1L ibru, 12.7% discontinued ibru and switched toacala or zanu. Median TTD in 1L was shorter for ibru than acala or zanu (Table). The associatedprobability of remaining on treatment was higher with zanu vs ibru or acala at months 6 and 12 (Table).
Median TTNT was not reached for zanu, while it was 30.2 months for ibru and 35.8 months for acala.
Conclusions: While zanu had relatively smaller sample size and shorter follow-up, this study
demonstrated better real-world safety and efficacy outcomes for acala and zanu vs ibru. Additional
research is needed to explain and validate observed differences favoring zanu over acala.
Table: TTD and TTNT in patients initiating BTKi therapies during index period
1L

Ibru (N=1389)
Median follow-up (range, mos)

TTD

Discont / Death (n, %)Median TTD (95% CI, mos)

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20.5 (0.4, 46.0)
775 (55.8)
13.7 (12.2, 16.0)

Acala(N=1223)
14.2 (0.1,46.0)
556 (45.5)
19.2 (15.1,25.3)

Zanu (N=203)
6 (1.1, 26.6)
45 (22.2)
19.3 (14.1,NR)

Prob of con�nuing same Tx at 6 mos
81.6 (75.1,64.8 (62.2, 67.3) 64.8 (62, 67.4)(%, 95% CI)
86.6)
Prob of con�nuing same Tx at 12 mos
57.7 (54.7,53.3 (50.5, 56)
64.1 (51, 74.6)(%, 95% CI)
60.6)
TTNT
NT / Death (n, %)617 (44.4)
457 (37.4)
37 (18.2)
Median TTNT (95% CI, mos)
30.2 (26.2, 35.5) 35.8 (29.8, NR) NR (16.7, NR)
Prob of con�nuing 1L Tx at 6 mos (%,71.3 (68.7,85.3 (79.2,75.4 (73, 77.6)
95% CI)
73.8)
89.8)
Prob of con�nuing 1L Tx at 12 mos (%,67.3 (64.6, 69.7) 66.3 (63.4, 69) 75 (64.3, 82.9)
95% CI)
1L, first line; acala, acalabrutinib; BTKi, Bruton tyrosine kinase inhibitor; CI, confidence interval; discont,discontinued; ibru, ibrutinib; mos, months; NR, not reached; NT, next treatment; prob, probability; TTD,time to treatment discontinuation; TTNT, time to next treatment; Tx, treatment; zanu, zanubrutinib.

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