Real-World Bruton Tyrosine Kinase Inhibitor Treatment Patterns and Outcomes
Among Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
in US Community Oncology Practices

P685

Jing-Zhou Hou,1 Simon Blanc,2 Gregory A. Maglinte,3 Anupama Vasudevan,2 Anna Rui,2 Mike Gart,2 Hoa Pham,3 Lindsay Aton,2 Brandon Wang,2 Rushir Choksi1
1UPMC, Pittsburgh, Pennsylvania, USA; 2Integra Connect, West Palm Beach, Florida, USA; 3BeiGene USA, Inc, San Mateo, CA, USA
RESULTS• Bruton tyrosine kinase inhibitors (BTKis) are now standard-of-care therapies for

Table 1. Demographics and Baseline Characteristics for 1L BTKi Patients••O BJ ECT IV E

• To investigate the clinical characteristics, treatment patterns, and AEs among BTKitreated patients with CLL/SLL in the real-world setting

MET HO DS
Data Source• IntegraConnect-PrecisionQ de-identified database of electronic health records, practicemanagement, and claims data from 55 practices and more than 1600 providers fromthe community oncology setting across the United States

Patient Population• Adults with CLL/SLL who initiated BTKi treatment between January 1, 2020 – January•

31, 2023 with follow-up through October 31, 2023
Patients had ≥5 CLL/SLL visits or more CLL/SLL visits than non-CLL/SLL visits; allpatients had ≥2 evaluation and management visits

Data Analysis• Descriptive analyses of structured electronic data
• Kaplan-Meier analyses were performed for time-to-event outcomes
Outcomes• Cardiovascular AEs• Time-to-next-treatment (TTNT): time from line of therapy (LOT) initiation to initiation of•next LOT or death
Time-to-treatment discontinuation (TTD) or death: time between treatment initiationand treatment discontinuation or deathR ESULTS
Figure 1. Disposition of Patients with CLL/SLL Initiated on Treatment Identified
During the Study
2815 initiated BTKi in 1L
6875
initiated 1L

Median age (range), years
Sex, n (%)
FemaleMale
Not documented/unknown/otherRace, n (%)
WhiteAfrican American
Asian
Not documented/unknown/other
ECOG status at index, n (%)
ECOG 0-1
ECOG 2+
N/A
Comorbidities, n (%)
Chronic pulmonary disease
Diabetes without chronic complications
Diabetes with chronic complications
Gastroesophageal reflux disease
Gastrointestinal disease
Iron-deficient anemia
Renal disease
Cardiac comorbidities, n (%)
All cardiac comorbidities
Acute ischemic heart disease
Angina pectoris
Atrial fibrillation
Atrial flutter
Cardiac arrest
Cardiac arrhythmia
Cardiomyopathy
Cardiotoxicity
Congestive heart failure
Hypertension
Ischemic stroke (cerebral infarction)
Left ventricular dysfunction
Myocardial infarction
Pulmonary arterial hypertension
StrokeVentricular tachycardia

Ibrutinib(n=1389)

Acalabrutinib(n=1223)

Zanubrutinib(n=203)71 (35, 90)

72 (36, 90)

72 (33, 90)

503 (36.2)
883 (63.6)
3 (0.2)450 (36.8)
770 (63)
3 (0.2)79 (38.9)
123 (60.6)
1 (0.5)842 (60.6)
98 (7.1)
10 (0.7)
439 (31.6)

775 (63.4)
60 (4.9)
6 (0.5)382 (31.2)

861 (62.0)
93 (6.7)435 (31.3)

750 (61.3)
91 (7.4)382 (31.2)

34 (2.4)
65 (4.7)
27 (1.9)61 (4.4)
105 (7.6)
66 (4.8)
57 (4.1)

127 (62.6)
9 (4.4)0 (0.0)67 (33)134 (66.0)
19 (9.4)
50 (24.6)

40 (3.3)
48 (3.9)
13 (1.1)
46 (3.8)
99 (8.1)
69 (5.6)
58 (4.7)230 (16.6)
2 (0.1)2 (0.1)44 (3.2)
2 (0.1)0 (0.0)10 (0.7)
7 (0.5)0 (0.0)4 (0.3)207 (14.9)
3 (0.2)1 (0.1)7 (0.5)0 (0.0)6 (0.4)4 (0.3)6 (3.0)5 (2.5)0 (0.0)5 (2.5)
10 (4.9)
6 (3.0)3 (1.5)192 (15.7)
1 (0.1)2 (0.2)38 (3.1)
0 (0.0)1 (0.1)2 (0.2)7 (0.6)0 (0.0)8 (0.7)172 (14.1)
6 (0.5)1 (0.1)10 (0.8)
1 (0.1)6 (0.5)0 (0.0)21 (10.3)
0 (0.0)0 (0.0)4 (2.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)2 (1.0)18 (8.9)
0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)ECOG PS, Eastern Cooperative Oncology Group; N/A, not available.

• The proportion of patients using zanubrutinib was greater in >1L of therapy than in 1L

249 initiated BTKi
in later lines

4060 initiated non-BTKi in 1LIbrutinib

Figure 2. BTKi Utilization

1389 (49.3%)

BTKi inlater line

99 (39.8%)

Zanubrutinib

Zanubrutinib

1223 (43.4%)203(7.2%)

42 (16.9%)

108 (43.4%)

Proportion of patients (%)

BTKi in 1L

Acalabrutinib

1510

115/790(14.6%)

118/972(12.1%)
99/1134(8.7%)
53/903(5.9%)

13/176(7.4%)

57/753(7.6%)

7/96(7.3%)

54/573(9.4%)

4/47(8.5%)

50%

20%

40%
60%
Proportion of patients

80%

100%

Acalabrutinib
Ibrutinib
Zanubrutinib

0.8

Table 3. Time to Next Treatment or Death in 1L BTKi0.60.4

Next treatment/death, n (%)
Median TTNT(95% CI), mo0.2
0.006

12182430

364263179
02196

537Time, months
Acalabrutinib
Ibrutinib
Zanubrutinib*P<.05FU, follow-up.

BTKi (6+ months FU)*

BTKi (9+ months FU)*outcomes for acalabrutinib and zanubrutinib vs ibrutinib
More patients experienced cardiovascular AEs when treated with ibrutinib thanacalabrutinib or zanubrutinib
The proportions of patients continuing treatment and the median TTNT waslonger for patients who received zanubrutinib
Additional research is needed to explain and validate observed differences
favoring zanubrutinib over acalabrutinib

Censored

1223
1389
203

716
870
85439
573
24261
404
6141278
2

Table 2. Time to Treatment Discontinuation or Death in 1L BTKiMedian durationof follow-up
from BTKi
initiation, mo
Discontinued/
death, n (%)
Censored, n (%)
Median TTD(95% CI), moOverall(n=2815)

Ibrutinib(n=1389)

Acalabrutinib(n=1223)

Zanubrutinib(n=203)-20.5 (0.4, 46.0)

14.2 (0.1, 46.0)

6 (1.1, 26.6)

1376 (48.9)775 (55.8)

556 (45.5)

45 (22.2)

1439 (51.1)

614 (44.2)

667 (54.5)

158 (77.8)

16.2 (14.4, 19.1)

13.7 (12.2, 16.0)

19.2 (15.1, 25.3)

19.3 (14.1, NR)

Probability of Continuing Same Treatment (95% CI), %6 mo

65.9 (64.1, 67.7)

64.8 (62.2, 67.3)

64.8 (62.0, 67.4)

81.6 (75.1, 86.6)

12 mo

56.1 (54.1, 58)

53.3 (50.5, 56.0)

57.7 (54.7, 60.6)

64.1 (51.0, 74.6)

18 mo

49.1 (47, 51.2)

46.2 (43.3, 49.0)

51.2 (48.0, 54.4)51 (30.5, 68.4)

24 mo

44 (41.7, 46.2)

40.9 (37.9, 43.8)

46.9 (43.3, 50.4)

42.5 (20.6, 62.9)

30 mo

39.8 (37.4, 42.3)

36.5 (33.5, 39.6)

43.9 (39.9, 47.8)

-

36 mo

34.6 (31.6, 37.6)

32.0 (28.6, 35.4)

37.0 (30.6, 43.3)

-

42 mo

32.6 (29.2, 36)

29.8 (26, 33.6)

37.0 (30.6, 43.3)-

Overall(n=2815)

Ibrutinib(n=1389)

Acalabrutinib(n=1223)

Zanubrutinib(n=203)1111 (39.5)

617 (44.4)

457 (37.4)

37 (18.2)

32.3 (29.1, 36.0)

30.2 (26.2, 35.5)

35.8 (29.8, NR)

NR (16.7, NR)

Probability of No Next Treatment (95% CI), %6 mo

74.3 (72.6, 75.9)

75.4 (73, 77.6)

71.3 (68.7, 73.8)

85.3 (79.2, 89.8)

12 mo

67.4 (65.6, 69.2)

67.3 (64.6, 69.7)

66.3 (63.4, 69.0)

75 (64.3, 82.9)

18 mo

60.9 (58.8, 62.8)

60.5 (57.7, 63.2)

60.3 (57.1, 63.3)

63.3 (46.1, 76.3)

24 mo

55.6 (53.4, 57.8)

54.9 (51.9, 57.7)

56.1 (52.6, 59.4)

57 (37.2, 72.6)

30 mo

51.4 (49, 53.8)

50.0 (46.9, 53.1)

53.9 (49.9, 57.6)-36 mo47.1 (44.2, 49.9)

45.8 (42.3, 49.2)

49.2 (43.5, 54.7)-42 mo42 (38.3, 45.5)

39.9 (35.7, 44)

49.2 (43.5, 54.7)-

1L, first-line; BTKi, Bruton tyrosine kinase inhibitor; CI, confidence interval; NR, not reached; TTNT, time-to-next treatment.

• Of patients treated with 1L ibrutinib, 12.7% discontinued ibrutinib and switched to a•second-generation BTKi
The median TTD in 1L was shorter for ibrutinib than acalabrutinib or zanubrutinib― The median TTD (95% CI) in the 1L setting was 13.7 (12.2, 16.0) months for ibrutinib,19.2 (15.1, 25.3) months for acalabrutinib, and 19.3 (14.1, NR) months for zanubrutinib• The associated probability of continuing treatment and not having new treatment•

were higher with zanubrutinib vs ibrutinib or acalabrutinib at month 6
The median TTNT (95% CI) was not reached (16.7, NR) for those who received
zanubrutinib in the 1L setting, while it was 35.8 (29.8, NR) months for acalabrutinib
and 30.2 (26.2, 35.5) months for ibrutinib

L IM ITATION S• Zanubrutinib had a relatively smaller sample size and shorter follow-up• Analyses were based only on structured dataCI, confidence interval; NR, not reached.

1.0

Acalabrutinib
Ibrutinib
Zanubrutinib

0.8

CensoredR E FE R E N CE S
1. NCCN. Clinical Practice Guidelines in Oncology. Chronic lymphocytic leukemia/small
lymphocytic lymphoma, v3. 2023.
2. Byrd JC, et al. J Clin Oncol. 2021;39(31):3441-3452.
3. Brown JR, et al. N Engl J Med. 2023;388(4):319-332.

0.60.4D ISCLOS U R E S

0.2J-ZH, RC: Consultant: BeiGene and Integra Connect. SB, AV, AR, MG, LA, BW: Employment:
Integra Connect. GAM, HP: Employment and may hold stock: BeiGene.

0.0612182430364278267034160

1064

Time, months
BTKi (3+ months FU)

••

1.000

•

Figure 4. Time to Discontinuation

Figure 5. Kaplan-Meier Curves for Time to Next Treatment or Death in 1L BTKi20Acalabrutinib•• This study demonstrated better real-world CLL/SLL safety and effectivenessAEs was highest in patients who initiated ibrutinib (8.7%), followed by zanubrutinib(7.4%), and acalabrutinib (5.9%)
Significantly more patients experienced cardiovascular AEs among those who
received 1L ibrutinib vs acalabrutinib or zanubrutinib at month 6 (12.1%, 7.6%, and 7.3%,respectively; P<.05) and at month 9 (14.6%, 9.4%, and 8.5%, respectively; P<.05)of therapy (Figure 2)

Figure 3. Cardiovascular AEs in the 1L Setting

Ibrutinib• Of patients within the first 3 months of follow-up post-BTKi initiation, the rate of cardiac

Proportion without next treatment•both first-line and second-line (1L/2L) relapsed/refractory (R/R) chronic lymphocytic
leukemia (CLL) and small lymphocytic leukemia (SLL)
National Comprehensive Cancer Network (NCCN) Guidelines list second-generation
BTKis zanubrutinib and acalabrutinib as preferred agents over first-generation BTKi
ibrutinib based on the toxicity profile1
Among high-risk patients with R/R CLL in the phase 3 ELEVATE-RR trial, progressionfree survival (PFS) with acalabrutinib was noninferior to that of ibrutinib2
The phase 3 ALPINE study in R/R CLL/SLL demonstrated superior PFS for zanubrutinib
compared with ibrutinib, and zanubrutinib was associated with fewer adverse events(AEs) leading to discontinuation, including fewer cardiac AEs and a lower rate of atrial
fibrillation3

CONCLU S ION S

Proportion on treatment

I NT RO DUC TI ON

Acalabrutinib
Ibrutinib
Zanubrutinib

1223
1389
203

791
1007
92515
738
32322
554
10177
407
3ACK NOWL E D G E M E NTSThis study was sponsored by BeiGene, Ltd. Editorial assistance was provided by SNELL
and was supported by BeiGene.

Presented at EHA 2024; June 13-16, 2024; Madrid, Spain/Virtual Conference