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
Jing-Zhou Hou, Simon Blanc, Gregory A. Maglinte, Anupama Vasudevan, Anna Rui, Mike Gart, Hoa Pham, Lindsay Aton, Brandon Wang, Rushir Choksi
1232223221

UPMC, Pittsburgh, Pennsylvania, USA; Integra Connect, West Palm Beach, Florida, USA; BeiGene USA, Inc, San Mateo, CA, USA
3RESULTS• Bruton tyrosine kinase inhibitors (BTKis) are now standard-of-care therapies for both first-line andsecond‑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, progression-free 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 withibrutinib, and zanubrutinib was associated with fewer adverse events (AEs) leading to discontinuation,
including fewer cardiac AEs and a lower rate of atrial fibrillation3

Table 1. Demographics and Baseline Characteristics for 1L BTKi Patients

OBJECTIVEMedian age (range), years

20

Ibrutinib(n=1389)

Acalabrutinib(n=1223)

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

72 (36, 90)

72 (33, 90)Sex, n (%)
Female503 (36.2)

450 (36.8)

79 (38.9)

Male883 (63.6)

770 (63)

123 (60.6)

3 (0.2)3 (0.2)1 (0.5)

Not documented/unknown/otherRace, n (%)• To investigate the clinical characteristics, treatment patterns, and AEs among BTKi-treated patients with
CLL/SLL in the real-world setting

METHODS
Data Source• IntegraConnect-PrecisionQ de-identified database of electronic health records, practice management, andclaims data from 55 practices and more than 1600 providers from the community oncology setting acrossthe United States

Patient Population

WhiteAfrican American

842 (60.6)
98 (7.1)775 (63.4)
60 (4.9)

127 (62.6)
9 (4.4)Asian

10 (0.7)

6 (0.5)0 (0.0)Not documented/unknown/other439 (31.6)

382 (31.2)

67 (33)

ECOG status at index, n (%)
ECOG 0-1

861 (62.0)

750 (61.3)

134 (66.0)

ECOG 2+93 (6.7)

91 (7.4)

19 (9.4)

N/A

435 (31.3)

382 (31.2)

50 (24.6)

Comorbidities, n (%)
Chronic pulmonary disease34 (2.4)

40 (3.3)

6 (3.0)

Data Analysis

Diabetes without chronic complications

65 (4.7)

48 (3.9)5 (2.5)Diabetes with chronic complications

27 (1.9)

13 (1.1)

0 (0.0)Gastroesophageal reflux disease61 (4.4)

46 (3.8)5 (2.5)Gastrointestinal disease

105 (7.6)

99 (8.1)

10 (4.9)• Time-to-next-treatment (TTNT): time from line of therapy (LOT) initiation to initiation of next LOT or deathIron-deficient anemia

66 (4.8)

69 (5.6)6 (3.0)• Time-to-treatment discontinuation (TTD) or death: time between treatment initiation and treatment
discontinuation or death

Renal disease

57 (4.1)

58 (4.7)

3 (1.5)• Kaplan-Meier analyses were performed for time-to-event outcomes

Outcomes• Cardiovascular AEs

Cardiac comorbidities, n (%)

RESULTSAll cardiac comorbidities

Figure 1. Disposition of Patients with CLL/SLL Initiated on Treatment Identified During the Study
2815 initiated BTKi in 1L
6875
initiated 1L

249 initiated BTKi
in later lines

4060 initiated non-BTKi in 1L

1L, first line; BTKi, Bruton tyrosine kinase inhibitor.

• The proportion of patients using zanubrutinib was greater in >1L of therapy than in 1L of therapy (Figure 2)
Figure 2. BTKi Utilization
BTKi infirst line

Ibrutinib

Acalabrutinib

Zanubrutinib

1389 (49.3%)

BTKi inlater line

99 (39.8%)

0%

20%

BTKi, Bruton tyrosine kinase inhibitor.

PRESENTER: Gregory A. Maglinte
Correspondence: Jng-Zhou Hou, houj@upmc.edu

203(7.2%)

1223 (43.4%)

42 (16.9%)

108 (43.4%)40%60%
Proportion of patients

80%

100%

230 (16.6)

192 (15.7)

Ibrutinib
Acalabrutinib
Zanubrutinib

118/972(12.1%)
1054/573(9.4%)

99/1134(8.7%)
53/903(5.9%)

57/753(7.6%)

13/176(7.4%)

BTKi (3+ months follow-up)• Of patients within the first 3 months of follow-up post-BTKi initiation, the rate of cardiac AEs 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 vsacalabrutinib 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)
Figure 4. Time to Discontinuation

21 (10.3)

1.0

Acalabrutinib
Ibrutinib
Zanubrutinib
Censored0.8
0.6
0.4
0.2
0.006

Number at risk
Acalabrutinib 1223716
Ibrutinib 1389
870
Zanubrutinib 203
85

1218
24
Time, months

0 (0.0)

Angina pectoris

2 (0.1)2 (0.2)0 (0.0)Atrial fibrillation

44 (3.2)

38 (3.1)

4 (2.0)Atrial flutter

2 (0.1)0 (0.0)0 (0.0)

Cardiac arrest

0 (0.0)1 (0.1)0 (0.0)

Cardiac arrhythmia

10 (0.7)

2 (0.2)0 (0.0)

Cardiomyopathy

7 (0.5)7 (0.6)0 (0.0)

Cardiotoxicity

0 (0.0)0 (0.0)0 (0.0)Congestive heart failure

4 (0.3)8 (0.7)2 (1.0)Hypertension

207 (14.9)

172 (14.1)

18 (8.9)

Probability of Continuing Same Treatment (95% CI), %Ischemic stroke (cerebral infarction)

3 (0.2)6 (0.5)0 (0.0)

6 mo

Left ventricular dysfunction

1 (0.1)1 (0.1)0 (0.0)0 (0.0)Pulmonary arterial hypertension

0 (0.0)1 (0.1)0 (0.0)Stroke6 (0.4)6 (0.5)0 (0.0)Ventricular tachycardia

4 (0.3)0 (0.0)0 (0.0)ECOG PS, Eastern Cooperative Oncology Group; N/A, not available.

BTKi (9+ months follow-up)**P<.05
BTKi, Bruton tyrosine kinase inhibitor.

1 (0.1)10 (0.8)

7/96(7.3%)

BTKi (6+ months follow-up)*

2 (0.1)7 (0.5)

4/47(8.5%)

5

Acute ischemic heart disease

Myocardial infarction• This study demonstrated better real-world CLL/SLL safety and effectiveness outcomes foracalabrutinib and zanubrutinib vs ibrutinib• More patients experienced cardiovascular AEs when treated with ibrutinib than acalabrutinib
or zanubrutinib• The proportions of patients continuing treatment and the median TTNT was longer for patients
who received zanubrutinib• Additional research is needed to explain and validate observed differences favoring zanubrutinib
over acalabrutinib

115/790(14.6%)

150• Adults with CLL/SLL who initiated BTKi treatment between January 1, 2020 – July 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; all patients had ≥2
evaluation and management visits• Descriptive analyses of structured electronic data

CONCLUSIONS

439
573
24261
404
614127823036426317902196537

Figure 5. Kaplan-Meier Curves for Time to Next Treatment or Death in 1L BTKi
Proportion on treatment

INTRODUCTION

Figure 3. Cardiovascular AEs in the 1L Setting

Proportion on treatment2

Proportion of patients (%)

11.0

Acalabrutinib
Ibrutinib
Zanubrutinib
Censored

0.8
0.6
0.4
0.2
0.0

006

12182430

36421223
1389
203

791
1007
92515
73832322554
10177
407
378
267034160

10646

Number at risk
Acalabrutinib 1223
791
Ibrutinib 1389
1007
Zanubrutinib 203
92121824Time, months

515
738
32322
554
10177
407
330364278
267
0341601064

Table 3. Time to Next Treatment or Death in 1L BTKi
Overall(n=2815)

Ibrutinib(n=1389)

Acalabrutinib(n=1223)

Zanubrutinib(n=203)

Next treatment/death, n (%)

1111 (39.5)

617 (44.4)

457 (37.4)

37 (18.2)

Median TTNT (95% CI), mo

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.

Table 2. Time to Treatment Discontinuation or Death in 1L BTKi

• Of patients treated with 1L ibrutinib, 12.7% discontinued ibrutinib and switched to a second-generation BTKi

Overall(n=2815)

Ibrutinib(n=1389)

Acalabrutinib(n=1223)

Zanubrutinib(n=203)• The median TTD in 1L was shorter for ibrutinib than acalabrutinib or zanubrutinib–

20.5 (0.4, 46.0)

14.2 (0.1, 46.0)

6 (1.1, 26.6)

Discontinued/death, n (%)

1376 (48.9)775 (55.8)

556 (45.5)

45 (22.2)

Censored, n (%)

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)• The associated probability of continuing treatment and not having new treatment were higher withzanubrutinib 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

65.9 (64.1, 67.7)

64.8 (62.2, 67.3)

64.8 (62.0, 67.4)

81.6 (75.1, 86.6)• Zanubrutinib had a relatively smaller sample size and shorter follow-up

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)• Analyses were based only on structured data

18 mo49.1 (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)

REFERENCES

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)-Median duration of follow-up from
BTKi initiation, moMedian TTD (95% CI), moCI, confidence interval; NR, not reached.

– 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

LIMITATIONS

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.

ACKNOWLEDGEMENTS

This study was sponsored by BeiGene, Ltd. Editorial assistance was provided by
SNELL and was supported by BeiGene.

3. Brown JR, et al. N Engl J Med. 2023;388(4):319-332.

DISCLOSURES

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

Presented at the 2024 Pan Pacific Lymphoma Conference; July 15-19, 2024, Lahaina, HI
Previously presented at EHA 2024; June 13-16, 2024; Madrid, Spain/Virtual Conference