RECENT PATTERNS OF CARE WITH BTK INHIBITORS AND DISTRIBUTION OF SOCIAL DETERMINANTS OF HEALTHAMONG PATIENTS WITH CLL/SLL IN THE US COMMUNITY SETTINGDavid J. Andorsky,¹ Thomas W. Wilson,² Kathleen M. Aguilar,² Chuck Wentworth,² Yunfei Wang,² Scott D. Goldfarb,³ Keri Yang,³ Erlene K. Seymour,³ Mark Balk,³ Gregory A. Maglinte,³ Ira Zackon²¹The US Oncology Network/Rocky Mountain Cancer Centers, Boulder, CO, USA; ²Ontada, Boston, MA, USA; ³BeiGene USA, Inc, San Mateo, CA, USAINTRODUCTIONTable 1. Demographics and Clinical Characteristics• Bruton tyrosine kinase (BTK) inhibitors, including ibrutinib, acalabrutinib, and zanubrutinib have been the mainstay treatments for patients with chronic
lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)1,2• In 2 recent randomized clinical trials, acalabrutinib and zanubrutinib demonstrated significantly longer progression-free survival compared with ibrutinib among
patients with relapsed or refractory CLL/SLL3,4• The aim of this study was to examine the characteristics, treatment patterns, and social determinants of health (SDOH) among patients with CLL/SLL who
received BTK inhibitors in a large network of community oncology practices

Overall(N=2082)

Acalabrutinib →no subsequent
BTK inhibitor(n=1159)

Ibrutinib →no subsequent
BTK inhibitor(n=628)

Zanubrutinib →no subsequent
BTK inhibitor(n=113)

Switched fromibrutinib →acalabrutinib(n=82)

Switched fromacalabrutinib →ibrutinib(n=62)

Switched fromacalabrutinib →zanubrutinib(n=38)

73 (21-90+)

73 (21-90+)

74 (28-90+)

74 (51-90+)

73 (40-89)

70.5 (40-89)

76.5 (44-90+)

Male1288 (61.9)716 (61.8)

387 (61.6)

78 (69.0)

50 (61.0)

35 (56.5)

22 (57.9)

Female794 (38.1)

443 (38.2)

241 (38.4)

35 (31.0)

32 (39.0)

27 (43.5)

16 (42.1)

Asian

17 (0.8)

7 (0.6)7 (1.1)0

1 (1.2)2 (3.2)0Black

178 (8.5)

93 (8.0)64 (10.2)

9 (8.0)5 (6.1)3 (4.8)4 (10.5)

White1530 (73.5)

860 (74.2)

454 (72.3)

81 (71.7)

59 (72.0)

47 (75.8)

29 (76.3)

Other

82 (3.9)49 (4.2)

23 (3.7)

3 (2.7)4 (4.9)3 (4.8)0No information

275 (13.2)

150 (12.9)

80 (12.7)

20 (17.7)

13 (15.9)

7 (11.3)

5 (13.2)

51 (2.4)

31 (2.7)

16 (2.5)

1 (0.9)1 (1.2)

1 (1.6)

1 (2.6)

Not Hispanic or Latino

1692 (81.3)

954 (82.3)

500 (79.6)

91 (80.5)

69 (84.1)

46 (74.2)

32 (84.2)

No information

339 (16.3)

174 (15.0)

112 (17.8)

21 (18.6)

12 (14.6)

15 (24.2)

5 (13.2)

Median age at index, y (range)

CONCLUSIONS• The results of this study indicate that the treatment landscape of BTK inhibitor use among patients with CLL/SLL is shifting, withincreased adoption of acalabrutinib and zanubrutinib over time
• Similarities in SDOH measures across the treatment sequence subgroups suggest that patients’ SES and Medicaid utilization do not
influence prescribing patterns• Differences across treatment subgroups regarding rural/urban status warrant further consideration

Sex, n (%)

METHODS• Further real-world investigations and longitudinal follow-up are needed to examine the impacts of SDOH on treatment choice,treatment switching, reasons for switching, and outcomes among users of BTK inhibitors

Race, n (%)• Study Design: A retrospective, observational cohort study• Data Source: Study data were sourced from structured fields of The US Oncology Network’s electronic healthcare record (EHR)–iKnowMed (iKM)–and theassociated claims database, the Financial Data Warehouse (FDW). EHR and FDW data were linked to the following external databases for evaluation of SDOH
measures:– The Neighborhood Atlas® for Area Deprivation Index (ADI) scores, which were determined by mapping patients’ home addresses to census block groups(CBGs), are based on the following socioeconomic factors: income, education, employment, and housing quality of residents within CBGs. Low socioeconomicstatus (SES) was defined as the top 20% of ADI scores on a national and state level (cut-off based on literature review)– The US Department of Agriculture’s rural/urban commuting area code database (these codes are based on population data from the 2020 census, the latest
urban area delineations from the Census Bureau, and updated community data from the American Community Survey)– Insurance coverage was reported as documented in the FDW, with Medicaid as an indicator of low SES• Overall, 137 patients (6.6%; 95% CI, 5.6-7.7) were classified as living in rural locations, and having low SES status based on state and national indicators wasobserved among 361 patients (17.3%; 95% CI, 15.7-19.0) and 125 (6.0%; 95% CI, 5.0-7.1), respectively• The highest proportion of patients had Medicare insurance coverage (42.1%; n=877; 95% CI, 40-44.3), followed by managed Medicare (24.4%; n=508;
95% CI, 22.6-26.3)• A statistical difference was found in treatment regimen groups classified by rural/urban status (P<.01), but not for state ADI (P=.52), national ADI (P=.36), orMedicaid insurance coverage vs all other coverage (P=.18) (Table 2)

Ethnicity, n (%)
Hispanic or Latino• Study Population: Adult patients with CLL/SLL whose first documented prescription for a BTK inhibitor occurred between January 1, 2020 and April 30, 2023.
Patients without a subsequent visit after BTK inhibitor initiation, those with inaccessible EHR data, those who received multiple BTK inhibitors on their treatment
initiation date, clinical trial participants, and those who received treatment for another primary cancer following treatment initiation were excluded. Patients were
followed until the last date of the study (April 30, 2023) or their last visit date, whichever occurred first• Statistical Analysis: Patients were stratified into mutually exclusive treatment sequence subgroups based on their immediate subsequent treatment following
index. Patient characteristics and SDOH measures were assessed descriptively, with Chi-squared P values reported for select SDOH measures. Data arepresented for treatment subgroups with at least 30 eligible patients

Table 2. SDOH by Treatment Sequence Subgroup• Demographic and clinical characteristics across the treatment sequences were similar, including sex, race, and ethnicity distributions, along with Rai stage andEastern Cooperative Oncology Group performance status scores at baseline (Table 1)• The highest proportion of patients received acalabrutinib, ibrutinib, or zanubrutinib, without an observed subsequent BTK inhibitor (n=1159 [55.7%], n=628[30.2%], and n=113 [5.4%], respectively) (Figure 1)• Temporal trends were observed in BTK inhibitor use over time across the 6 included subgroups (Figure 2)

Stage 0405 (19.5)

225 (19.4)

120 (19.1)

23 (20.4)

22 (26.8)

10 (16.1)

5 (13.2)

Stages I and II

551 (26.5)

315 (27.2)

146 (23.2)

32 (28.3)

24 (29.3)

22 (35.5)

12 (31.6)

Stages III and IV

565 (27.1)

339 (29.2)

146 (23.2)

30 (26.5)

21 (25.6)

18 (29.0)

11 (28.9)

No information

561 (26.9)

280 (24.2)

216 (34.4)

28 (24.8)

15 (18.3)

12 (19.4)

10 (26.3)

0334 (16.0)

180 (15.5)

102 (16.2)

18 (15.9)

17 (20.7)

13 (21.0)

4 (10.5)

1582 (28.0)

343 (29.6)

160 (25.5)

27 (23.9)

21 (25.6)

15 (24.2)

16 (42.1)

2+

123 (5.9)

72 (6.2)

37 (5.9)8 (7.1)5 (6.1)1 (1.6)01043 (50.1)

564 (48.7)

329 (52.4)

60 (53.1)

39 (47.6)

33 (53.2)

18 (47.4)

2020

597 (28.7)

204 (17.6)

331 (52.7)

1 (0.9)41 (50.0)

13 (21.0)

7 (18.4)2021

663 (31.8)

388 (33.5)

199 (31.7)

12 (10.6)

31 (37.8)

18 (29.0)

15 (39.5)2022

616 (29.6)

447 (38.6)

84 (13.4)

41 (36.3)

10 (12.2)

25 (40.3)

9 (23.7)2023

206 (9.9)120 (10.4)

14 (2.2)

59 (52.2)

06 (9.7)

7 (18.4)

14.1 (0-41)

12.7 (0-40.7)

19.9 (0-41.0)

3.7 (0-31.8)

22.6 (0.5-41.0)

12.9 (0.5-40.0)

18.5 (1.4-38.6)

No information

Adult patients diagnosed with CLL or SLL
N=31,212

Median follow-up duration (range), mos

0.2
2020
(n=597)
Year of BTK inhibitor initiation

34.2

961
(82.9, 80.6-85.0)546(86.9, 84.1-89.5)

94(83.2, 75.0-89.6)

72(87.8, 78.7-94.0)

49(79.0, 66.8-88.3)

27(71.1, 54.1-84.6)

Rural

137
(6.6, 5.6-7.7)

83(7.2, 5.7-8.8)

25(4.0, 2.6-5.8)

13(11.5, 6.3-18.9)

4(4.9, 1.3-12.0)

6(9.7, 3.6-19.9)

6(15.8, 6.0-31.3)

No information

196(9.4, 8.2-10.8)

115(9.9, 8.3-11.8)

57(9.1, 7.0-11.6)

6(5.3, 2.0-11.2)

6(7.3, 2.7-15.3)

7(11.3, 4.7-21.9)5(13.2, 4.4-28.1)–

Low SES (state), n (%, LL-UL)

361(17.3, 15.7-19.0)

195(16.8, 14.7-19.1)

109(17.4, 14.5-20.6)

22(19.5, 12.6-28.0)

12(14.6, 7.8-24.2)

13(21.0, 11.7-33.2)

10(26.3, 13.4-43.1).5195

Low SES (national), n (%, LL-UL)

125(6.0, 5.0-7.1)

69(6.0, 4.7-7.5)

40(6.4, 4.6-8.6)10(8.8, 4.3-15.7)

1(1.2, 0-6.6)

3(4.8, 1.0-13.5)2(5.3, 0.6-17.8).3603

Medicaid

73(3.5, 2.8-4.4)

38(3.3, 2.3-4.5)

22(3.5, 2.2-5.3)

3(2.7, 0.6-7.6)

3(3.7, 0.8-10.3)

5(8.1, 2.7-17.8)

2(5.3, 0.6-17.8)

Medicare877(42.1, 40.0-44.3)

481(41.5, 38.7-44.4)

265(42.2, 38.3-46.2)

52(46.0, 36.6-55.7)

40(48.8, 37.6-60.1)

24(38.7, 26.6-51.9)

15(39.5, 24.0-56.6)

Managed Medicare

508(24.4, 22.6-26.3)

275(23.7, 21.3-26.3)

158(25.2, 21.8-28.7)

30(26.5, 18.7-35.7)

17(20.7, 12.6-31.1)

10(16.1, 8.0-27.7)

18(47.4, 31.0-64.2)

Commercial

226(10.9, 9.6-12.3)

115(9.9, 8.3-11.8)

80(12.7, 10.2-15.6)

12(10.6, 5.6-17.8)8(9.8, 4.3-18.3)

10(16.1, 8.0-27.7)

1(2.6, 0.1-13.8)

No information

398(19.1, 17.5-20.9)

250(21.6, 19.2-24.1)

103(16.4, 13.6-19.5)

16(14.2, 8.3-22.0)

14(17.1, 9.7-27.0)

13(21.0, 11.7-33.2)

2(5.3, 0.6-17.8)

55.4

6.9

2021
(n=663)58.5

2022(n=616)

30.0

72.6

2.2b2023(n=206)

58.3

6.8

6.7

28.6

Strengths of the Study

1.5

Limitations

1.6 4.1

2.9 3.4

20

30

40

50
60
Percentage of patients

Zanubrutinib only
Ibrutinib only
Acalabrutinib onlyaBTK, Bruton tyrosine kinase.

Acalabrutinib → Zanubrutinib
Acalabrutinib → Ibrutinib
Ibrutinib → Acalabrutinib

7080

90100.182– atients’ ADI rank based on a scale of 1-10 (deciles) was based on their census block group; the top 20% of overall national and state scores was classified as being low SES. bManaged Medicare insurance coverage is provided byPcommercial insurance plans that work with Medicare.
ADI, Area Deprivation Index; BTK, Bruton tyrosine kinase; LL, lower limit; UL, upper limit; SDOH, Social Determinants of Health; SES, socioeconomic status.

• The study leveraged real-world clinical data from patients treated in The US Oncology Network practices, which represents a sizable proportion of patientswith cancer in the US• The iKM EHR has been deployed across all of The US Oncology Network practices, facilitating a homogenized dataset for research• As data for this study were originally recorded for clinical practice purposes, errors of omission and commission may be present in the dataset• The study design did not have a minimum follow-up time; therefore, there is a potential of differential follow-up time for patients who initiated BTK inhibitors
earlier in the study compared with those who initiated them later• This study utilized an intent-to-treat approach, which assumed that all prescribed oral therapies were taken, although this could not be verified withstructured data alone• Results are most generalizable for community oncology practices that utilize the iKM EHR and decision–support technology

REFERENCESACKNOWLEDGMENTS

1. Karr M, Roeker L. Cancers (Basel). 2023;15(4):1018.

10.0015a2.3
4.7 2.7

13.6

P value

Payor distribution, n (%, LL-UL)

1.2

1.8

Exclusion of patients in a treatment sequence subgroup less than 30 patientsa
n=2082

PRESENTER: Mark BalkCORRESPONDENCE: David Andorsky, david.andorsky@usoncology.com

1749(84.0, 82.4-85.6)

aFigure 2. Changes in BTK Inhibitor Use Between 2020 and 2023

0Per protocol, the analyses were limited to subgroups with at least 30 patients for 2 reasons: 1) results with <30 patients may result in small cell sizes, which is associated with a risk of re-identification, and2) subgroups of <30 patients would have been insufficient for statistical analyses.
BTK, Bruton tyrosine kinase; CLL, chronic lymphocytic leukemia; SLL, small lymphocytic lymphoma.

Switched fromacalabrutinib →zanubrtuinib(n=38)

aFollow-up was assessed from the first prescription for a BTK inhibitor during the study identification period until the end of the study observation period, date of last visit, or date of death, whichever occurred first.
BTK, Bruton tyrosine kinase; CLL, chronic lymphocytic leukemia; ECOG, Eastern Cooperative Oncology Group; mo, month; SLL, small lymphocytic lymphoma; y, year.

Patients with 1 subsequent visit after BTK inhibitor initiation
n=3583

Exclusion of patients who received multiple BTK inhibitor prescriptions at initiation
n=2104

Switched fromacalabrutinib →ibrutinib(n=62)

UrbanaExclusion of patients who received multiple BTK inhibitors prior to 01/01/20
n=2112

Switched fromibrutinib →acalabrutinib(n=82)

Rural/urban status category, n (%, LL-UL)

Index treatment year, n (%)

Figure 1. Study Attrition and Treatment Sequence Subgroups

Exclusion of patients who received treatment for another primary cancer
n=3290

Zanubrutinib →no subsequent
BTK inhibitor(n=113)Overall(N=2082)

ECOG performance status at baseline, n (%)• In total, 2082 patients were identified across 6 treatment sequence subgroups, each having at least 30 patients (Figure 1)

Exclusion of clinical trial participants
n=3456

Ibrutinib →no subsequent
BTK inhibitor(n=628)Rai stage, n (%)

RESULTS

Patients who initiated treatment with a BTK inhibitor between 01/01/20-04/30/23
n=3647

Acalabrutinib →no subsequent
BTK inhibitor(n=1159)

2. US Food & Drug Administration. FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic
lymphoma. Accessed May 10, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approveszanubrutinib-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma.

This study was sponsored by BeiGene, Ltd. Editorial assistance was provided by Nucleus Global, an
Inizio company, and supported by BeiGene.

3. Brown JR, et al. N Engl J Med. 2023;388(4):319-332.
4. Byrd JC, et al. J Clin Oncol. 2021;39(31):3441-3452.

DISCLOSURESIZ: Consultancy: Epizyme, MorphoSys. DA: Consultancy: AbbVie, AstraZeneca. TW, KA, CW: Employment:McKesson; Consultancy: BeiGene. YF: nothing to disclose. SG, KY, EKS, MB, GAM: Employment: BeiGene.

Presented at the 2024 Pan Pacific Lymphoma Conference; July 15-19, 2024, Lahaina, HI
Previously presented at the 28th Annual International Congress on Hematologic Malignancies; February 29-March 3, 2024, Miami Beach, FL