Real-World Treatment Switching and Sequencing to Next Line of Therapyof Zanubrutinib, Acalabrutinib, and Ibrutinib in CLL/SLLP697

Javier Pinilla-Ibarz,1 Mei Xue,2 Elizabeth Wu,3 Kaitlyn Esselman,3 Wesley Furnback,3 Swetha Challagulla,2 Keri Yang2
1Moffitt Cancer Center, Tampa, FL, USA; 2BeiGene, San Mateo, CA, USA; 3Real Chemistry, New York, NY, USA
I N T R OD U C T I O N

RE SU LTS

• Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) accountTable 1. Baseline Characteristics for Patients Initiating a BTKi in 1L

for 25% of all leukemia cases and although indolent, are considered incurable1,2

C ON C LU S I ON S

O B JE C T I V E

Variable

period between January 1, 2020 and February 28, 2023

Median (IQR), years

71 (63, 78)

70 (63, 78)

72 (65, 78)

762 (61.6)
460 (37.2)

Medicare/Medicaid

508 (43.2)

595 (44.1)

61 (39.1)

Other

433 (36.8)

524 (38.9)

57 (36.5)

Self pay

27 (2.3)

25 (1.9)

2 (1.3)1104 (89.2)
134 (10.8)
126 (10.2)

11 (7.0)II

58 (4.7)

78 (5.5)5 (3.2)

III74 (6.0)85 (6.0)

3 (1.9)IV

102 (8.2)

117 (8.2)

4 (2.6)N/A

779 (62.9)932 (65.6)

123 (78.3)

respectively

Acalabrutinib(n=672)

Ibrutinib(n=474)

Zanubrutinib(n=107)

Mean (SD), years

68.2 (10.1)

68.7 (9.6)

71.7 (10.2)

Median (IQR), years

68.5 (62, 76)

69 (62, 76)

71 (65, 80)

Gender, n (%)
Male

414 (61.6)

283 (59.7)

65 (60.8)

Female252 (37.5)

188 (39.7)

42 (39.3)• In 2L, acalabrutinib (53.6%) was the most commonly utilized BTKi followed byMedicare/Medicaid

275 (42.4)

186 (41.2)

47 (44.8)

Other

256 (39.5)

206 (45.6)

37 (35.2)

Self pay

11 (1.7)

8 (1.8)0 (0)• There were no significant differences across the 3 groups for age, gender, payer

type, or Rai stage at baseline among 1L patients (Table 1). There was a significant(P<.0001) difference in CLL vs SLL and zanubrutinib had the highest percentage of
SLL patients (26.75%)• Mean age at index was significantly different across the 3 BTKis (P=.0037)

with zanubrutinib having the highest mean age (Table 2). The percentage of CLL
vs SLL patients was also significantly (P<.0001) different among 2L patients withzanubrutinib having the highest percentage (24.3%) of SLL patients

10.2%

7.5%

Ibrutinib(n=1421)

Zanubrutinib(n=157)

Acalabrutinib(n=672)

1L*Ibrutinib(n=474)

Zanubrutinib(n=107)

United States, it is crucial to recognize that the results may not be applicable to all
populations• Although real-world data has gained acceptance as a reliable source forunderstanding actual practice patterns, it may present inherent data limitations
related to the completeness of the data source

2L*<60 days

REFERENCES

61-89 days

* P<.0001

1. Siegel RL, et al. CA Cancer J Clin. 2022;72(1):7-33.

• The proportion of patients receiving the next line of therapy at 180 days for2. Mukkamalla SKR, et al. Chronic Lymphocytic Leukemia. In: StatPearls.
Treasure Island (FL): StatPearls Publishing; March 7, 2023.

1L and 2L BTKis are shown in Figure 2P Value

CLL/SLL, n (%)• Among 1L patients, the proportion of receiving the next line of therapy atD ISCLOSU RES• In 2L, the proportion at 180 days of receiving the next line of therapy was 9.1% for

JP: Consultancy: Novartis, AbbVie, AstraZeneca, Takeda, Merck, Beigene, Eli Lilly,
Janssen; Speaker’s Bureau: AbbVie, Janssen, Takeda, AstraZeneca; Resesarch
Funding: MEI, TG Therapeutics
MX, SC, KY: Employment: Beigene
EW, KE, WF: Employment: Real Chemistry

180 days was 13.9% for zanubrutinib compared to 24.5% for acalabrutinib
and 21.1% for ibrutinib
zanubrutinib compared to 18.6% for acalabrutinib and 29.2% for ibrutinib.0663

Figure 2. Proportion of Patients Receiving Next Line of Therapy at 180 Days
1L or 2L BTKi
30.00%

CLL

602 (89.6)

376 (79.3)

81 (75.7)

SLL

70 (10.4)

98 (20.7)

26 (24.3)

Rai stage, n (%)

24.5%
20.00%

21.1%
18.6%
13.9%

10.00%.0532

054 (8.0)

21 (4.4)5 (4.7)I

51 (7.6)

36 (7.6)

12 (11.2)

II

45 (6.7)

20 (4.2)

4 (3.7)III

54 (8.0)28 (5.9)4 (3.7)IV

61 (9.1)

50 (10.6)

4 (3.7)N/A

407 (60.6)

319 (67.3)

78 (72.9)

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

29.2%<.0001

IQR, interquartile range; SD, standard deviation.

LI M I TATI ON S

• While this study included a diverse cross-section of CLL/SLL patients in the

10.7%
7.5%

Acalabrutinib(n=1238).8045

21 (20)799) days for acalabrutinib, and 524 (259, 856) days for ibrutinib (P<.0001)

17.1%

0.0%.0037

52 (11.5)• In 2L, median (IQR) follow-up was 133 (62, 385) days for zanubrutinib, 503 (265,17.1%

zanubrutinib vs acalabrutinib and ibrutinib (1L P=.2958; 2L P<.0001)

106 (16.4)

406 (196, 659) days for acalabrutinib, and 637 (326, 921) days for ibrutinib (P<.0001)

2.5%• The proportion of patients receiving next line of therapy at 180 days was lower forCommercial• In 1L, median (IQR) follow-up was 123 (63, 335) days for zanubrutinib,10.2%

5.0%

2L(n=1253)• In 1L, ibrutinib (50.5%) was the most common BTKi followed by acalabrutinib (44.0%)
ibrutinib (37.8%) and zanubrutinib (8.54%)

emerging therapies and to assess long-term real-world outcomes

13.2%

13.1%

Table 2. Baseline Characteristics for Patients Initiating a BTKi in 2L

Payer type, n (%)

and zanubrutinib (5.6%)

BTKis in patients with CLL/SLL• Future studies with extended follow-up are necessary to facilitate evaluation of

2.5%

10.0%

IQR, interquartile range; SD, standard deviation.

Age at index

3.4%

15.0%

11 (7.0)

93 (6.5)• Sequencing to next line of therapy was calculated from the time-to-next treatment• A total of 2816 and 1253 patients initiated a 1L or 2L BTKi during the index period,

116 (8.2)

comprehensive assessment of treatment outcomes associated with use ofBTKis in CLL/SLL• This study highlighted the real-world advantages of zanubrutinib compared to other

4.0%
15.6%

42 (26.8)

99 (8.0)

Variable

20.0%

115 (73.3)

161 (11.3)• Longer follow-up and a larger zanubrutinib sample size are required for a

D I S C U S S I ON

21.1%.238• Demographics, clinical characteristics, and comorbidities were measured

R E S U LTS

1260 (88.7)

and lower proportion of patients receiving next line of therapy at 180 days
when compared with acalabrutinib and ibrutinib in 1L and 2L

25.0%<.0001I• Treatment switching was measured as patients initiating another treatment within

13.2% for acalabrutinib and 21.1% for ibrutinib among 2L patients

20.4%.1667
36 (23.1)

at baseline• Zanubrutinib also had the lowest switch rate before 90 days (7.5%) compared to52 (33.1)

Rai stage, n (%)

Cohorts

Kaplan-Meier curve, censoring patients at end of follow-up, and reported as theproportion of patients receiving next line of therapy at 180 days

532 (37.4)
204 (15.1)

0zanubrutinib (10.2%) compared to acalabrutinib (20.5%) and ibrutinib (15.6%)

104 (66.2)

208 (17.7)

SLL• Continuous enrollment in the database for ≥30 days prior to and after the index datesame line or advancing to next line of therapy within 90 days

881 (62)• In 1L, the percentage of patients switching before 90 days was lowest for• Zanubrutinib patients had significantly lower switching rates within 90 days

Figure 1. Treatment Switching for Patients Initiating a BTKi in 1L or 2L.2586

CommercialCLLindex period

Study Measures

70.4 (11.2)

CLL/SLL, n (%)

Inclusion Criteria• Cohorts were developed based on treatment regimens and stratified by line oftherapy (1L and 2L)― Acalabrutinib― Ibrutinib― Zanubrutinib

70.1 (10.4)

Payer type, n (%)• The study period was from December 1, 2019 to March 31, 2023 with an index

P Value.9168

70.1 (10.4)

Femaleincludes electronic medical records from community-based oncology practices• Age ≥18 years with ≥1 diagnosis for CLL or SLL• Initiated acalabrutinib, ibrutinib, or zanubrutinib in the 1L or 2L setting during theZanubrutinib(n=157)

Mean (SD), years

Male• A retrospective study was conducted using the Integra Connect database, which• Patients were indexed on the date of BTKi initiation during the index period

Ibrutinib(n=1421)

Gender, n (%)

METHODS
Data Source

Acalabrutinib(n=1238)

Age at index• The objective of this study was to evaluate real-world switching and sequencing tonext line of therapy in patients initiating BTKis as first-line (1L)or second-line (2L) CLL/SLL treatment

significantly lower for patients receiving zanubrutinib vs acalabrutinib and ibrutinib(P<.0001, both 1L and 2L) (Figure 1)

1L(n=2816)• Evaluating use of Bruton tyrosine kinase inhibitors (BTKis) for the treatment of CLL/SLL is crucial to understand real-world outcomes of these therapies in diverse
populations• Regardless of line of therapy, switching rate at ≤60 days and 61-89 days was

9.1%

0.00%
Acalabrutinib(n=1238)

Ibrutinib(n=1421)

1L*

Zanubrutinib(n=157)

Acalabrutinib(n=672)

Ibrutinib(n=474)

Zanubrutinib(n=107)

2L** P<.0001

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