Study design

SEQUOIA is an international, phase 3, open-label, randomised study of BRUKINSA^®▼ compared with bendamustine plus rituximab (BR) in patients with previously untreated CLL.^1–3 The study comprises 3 cohorts, as shown in Figure 1.^1–3

Cohorts 1 and 2 are complete, however Cohort 3 is ongoing.^1–3

Figure 1. SEQUOIA study design.^1–3

CLL, chronic lymphocytic leukaemia; SLL, small lymphocytic lymphoma. Treatment continued until disease progression or unacceptable toxicity.

Patients

Patients had previously untreated CLL/SLL, ≥65 years of age or <65 years of age and unsuitable for chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR).^1,4

Stratification

In Cohort 1, randomisation was stratified by age (<65 years versus ≥65 years), Binet stage (C versus A or B), immunoglobulin variable region heavy chain (IGHV) mutational status (mutated versus unmutated), and geographic region (North America versus Europe versus Asia-Pacific).^1,4

Key baseline characteristics

Cohort 1
Cohort 2
Cohort 3

The key baseline characteristics for Cohort 1 are summarised below in Table 1.

Table 1. SEQUOIA: Key baseline characteristics for Cohort 1 (patients without del[17p]).¹

	BRUKINSA (n=241)	Bendamustine + rituximab (n=238)
Median (IQR) age, years	70 (66–75)	70 (66–74)
<65	45 (19%)	46 (19%)
≥65*	196 (81%)	192 (81%)
Race or ethnicity, n (%)
White	221 (92%)	206 (87%)
Black	4 (2%)	4 (2%)
Asian or Pacific Islander	5 (2%)	9 (4%)
Not reported or unknown	11 (5%)	22 (9%)
Binet stage,^† n (%)
A/B	171 (71%)	168 (71%)
C	70 (29%)	70 (29%)
Bulky disease ≥5 cm , n (%)	69 (29%)	73 (31%)
Cytopenia at baseline,^‡ n (%)	102 (42%)	109 (46%)
del(17p)	2 (1%)^§	0
del(11q)	43 (18%)	46 (19%)
del(13q)	136 (56%)	129 (54%)
Trisomy 12	45 (19%)	49 (21%)
Unmutated IGHV gene	125/234 (53%)	121/231 (52%)
No FISH abnormalities^\|\|	56 (23%)	59 (25%)
TP53 mutation	15/232 (6%)	13/223 (6%)

FISH, fluorescence in situ hybridisation; IQR, interquartile range. *Patients ≥75 years: 63 patients in the BRUKINSA group (26%) and 53 patients in bendamustine + rituximab group (22%). ^†Patients with SLL had Binet stage calculated as if they had CLL. ^‡Defined as having anaemia (haemoglobin ≤110 g/L), thrombocytopenia (platelets ≤100 × 10⁹/L), or neutropenia (absolute neutrophil count ≤1.5 × 10⁹/L). ^§Two patients with del(17p) were misassigned to the randomly assigned cohort of patients without del(17p). These patients are included in the intention-to-treat analysis. ^||Defined as the absence of del(17p), del(11q), del(13q), and trisomy 12. Adapted from Tam CS, et al. Lancet Oncol. 2022.¹

The key baseline characteristics for Cohort 2 are summarised below in Table 2.

Table 2. SEQUOIA: Key baseline characteristics for Cohort 2 (patients with del[17p]).¹

	BRUKINSA (n=111)
Median (IQR) age, years	70 (66–74)
<65	16 (14%)
≥65*	95 (86%)
Race or ethnicity, n (%)
White	105 (95%)
Black	0
Asian or Pacific Islander	1 (1%)
Not reported or unknown	5 (5%)
Binet stage,^† n (%)
A/B	72 (65%)
C	39 (35%)
Bulky disease ≥5 cm , n (%)	44 (40%)
Cytopenia at baseline,^‡ n (%)	61 (55%)
del(17p)	110 (99%)^§
del(11q)	37 (33%)
del(13q)	74 (67%)
Trisomy 12	20 (18%)
Unmutated IGHV gene	67/103 (60%)
No FISH abnormalities^\|\|	0
TP53 mutation	47/109 (43%)

FISH, fluorescence in situ hybridisation; IQR, interquartile range. *Patients ≥75 years: 63 patients in the BRUKINSA group (26%) and 53 patients in bendamustine + rituximab group (22%). ^†Patients with SLL had Binet stage calculated as if they had CLL. ^‡Defined as having anaemia (haemoglobin ≤110 g/L), thrombocytopenia (platelets ≤100 × 10⁹/L), or neutropenia (absolute neutrophil count ≤1.5 × 10⁹/L). ^§One patient without del(17)(p13·1) was misassigned to the non-randomly assigned cohort of patients with del(17)(p13·1). The patient is excluded from the efficacy analysis of this cohort. ^||Defined as the absence of del(17p), del(11q), del(13q), and trisomy 12. Adapted from Tam CS, et al. Lancet Oncol. 2022.¹

Cohort 3 is currently ongoing, however preliminary results are promising.^2,3

A total of 35 patients had been enrolled at the time of data cutoff (June 1, 2021), with a median follow-up of 9.7 months.³

Table 3 summarises the preliminary summary of safety and efficacy at data cutoff.

Table 3. SEQUOIA: Cohort 3 summary of preliminary results.³

Efficacy	Cohort 3 (n=31)*
Median follow-up, months	11.2
Overall response rate (CR/CRi, PR, or PR-L), n (%) [95% CI]	30 (96.8) [69.7, 95.2]
CR/CRi, n (%)	4 (12.9)
PR, n (%)	22 (71.0)
PR-L, n (%)	4 (12.9)

Efficacy	Cohort 3 (n=35)
Median follow-up, months	9.72
Any adverse event, n (%)	29 (82.9)
Grade 3 or higher adverse event, n (%)	13 (37.1)
Serious adverse event, n (%)	4 (11.4)
Treatment discontinuation due to adverse event, n (%)	1 (2.9)

CI, confidence interval; CR, complete response; CRi, CR with bone marrow recovery; PR, partial response; PR-L, PR with lymphocytosis. *Data shown are for the 31 patients who reached the initial efficacy assessment at 3 months after starting BRUKINSA. Adapted from Tedeschi AT, et al. ASH 2021.³

Primary endpoint

In the SEQUOIA study, independent review committee (IRC)-assessed PFS in Cohort 1 (patients without del[17p]) was the primary endpoint and was met at the interim analysis.^1,4 PFS was significantly longer with BRUKINSA compared with BR (Figure 2).^1,4

At 24 months, the estimated PFS rate in Cohort 1 was 85.5% (95% CI: 80.1, 89.6) for BRUKINSA versus 69.5% (95% CI: 62.4, 75.5) for BR .^1,4After a median follow up of 26.2 months, the IRC determined that PFS was significantly improved with BRUKINSA versus BR (HR 0.42 [95% CI: 0.28 to 0.63]; two-sided p<0.0001; Figure 2).^1,4

Figure 2. SEQUOIA: Kaplan-Meier estimates of IRC-assessed PFS for Cohort 1 (patients without del[17p]).^1,4

CI, confidence interval; HR, hazard ratio; IRC, independent review committee; PFS, progression-free survival. Adapted from Tam CS, et al. *Lancet Oncol*. 2022.¹

In Cohort 1, PFS was consistently longer with BRUKINSA compared with BR across almost all prespecified subgroup analyses, including patients with baseline high-risk disease status (Figure 3).¹

Figure 3. SEQUOIA: IRC-assessed PFS across subgroups for BRUKINSA versus BR in Cohort 1 (patients without del[17p]).¹

BR, bendamustine + rituximab; CI, confidence interval; *IGHV*, immunoglobulin heavy chain variable; IRC, independent review committee; PFS, progression-free survival. Adapted from Tam CS, et al. *Lancet Oncol*. 2022.¹

Key secondary endpoints

Investigator-assessed (IA) PFS for Cohorts 1 and 2 was a key secondary endpoint in SEQUOIA and was found to be consistent with IRC-assessed PFS.¹ An updated analysis was conducted after a median follow up of 43.7 months for Cohort 1.⁵ Median IA-PFS was not reached in the BRUKINSA group compared with 42.2 months in the BR group group.⁵ Estimated 42-month PFS rates were 82.4% for BRUKINSA and 50.0% for BR.⁵ IA-PFS was significantly improved with BRUKINSA versus BR with mutated IGHV (2-sided, p=0.00033) and unmutated IGHV (2-sided p=0.0001).⁵ The median follow up for Cohort 2 was 47.9 months.⁵ Median IA-PFS for Cohort 2 was not reached and the estimated 42 month rate was 79.4%.⁵

ORR for Cohorts 1 and 2 was a key secondary endpoint in the SEQUOIA study.^1,4

In Cohort 1 (patients without del[17p]), IRC-assessed ORR, was 94.6% (228/241; 95% CI: 91.0, 97.1) in the BRUKINSA group, and 85.3% (203/238; 95% CI: 80.1, 89.6) in the BR group.^1,4In the BRUKINSA group, 16 (7%) of 241 patients had a complete response, as assessed by IRC, versus 36 (15%) of 238 patients in the BR group.¹

For Cohort 2 (patients with del[17p]) IRC-assessed ORR was 90.0% (99/110; 95% CI: 82.8, 94.9).¹

Safety

Cohort 1
Cohort 2

A total of 93% (224/240) of patients in the BRUKINSA group and 94% (214/227) of patients in the BR group experienced an adverse event.⁶

Serious adverse events occurred in 37% (88/240) of patients in the BRUKINSA group and 50% (113/227) of patients in the BR group¹

The most common adverse events occurring in the BRUKINSA group were contusion (19%) and upper respiratory tract infection (17%)⁶

Adverse events, common adverse events, and adverse events of special interest are shown in
tables 4–6.

Table 4. SEQUOIA Cohort 1 adverse events (n, %).^1,6

Any adverse event	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	98 (41)	37 (16)
Grade 3	87 (36)	88 (39)
Grade 4	28 (12)	81 (36)
Grade 5	11 (5)	12 (5)‡
Serious	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	16 (7)	12 (5)
Grade 3	49 (20)	70 (31)
Grade 4	12 (5)	19 (8)
Grade 5	11 (5)	12 (5)
All bleeding adverse events^§	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	99 (41)	21 (9)
Grade 3	8 (3)	3 (1)
Grade 4	0	1 (<1)
Grade 5	1 (<1)	0
All cardiac adverse events^§	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	24 (10)	13 (6)
Grade 3	10 (4)	9 (4)
Grade 4	0	1 (<1)
Grade 5	2 (1)	1 (<1)
Dose reduction due to AEs	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
All Grades	20 (3)	85 (37)
Discontinuation due to AEs	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
All Grades	20 (8)	31 (14)

*One patient in the BRUKINSA group did not receive BRUKINSA and is not included in the safety analysis.^†11 patients did not receive bendamustine + rituximab and are not included in the safety analysis. ^‡Includes one patient who had a Grade 5 event (confusion) that began prior to, but ended, after the data cutoff.^§Grouped analyses. Adapted from Tam CS, et al. Lancet Oncol. 2022, and Supplemntary appendix.^1,6

Table 5. SEQUOIA Cohort 1 common adverse events.¹

Contusion	BRUKINSA (n=240*)	Bendamustine + rituximab (n=227^†)
Grade 1-2	46 (19)	8 (4)
Grade 3	0	0
Grade 4	0	0
Grade 5	0	0
Upper respiratory tract infection	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	39 (16)	25 (11)
Grade 3	2 (1)	2 (1)
Grade 4	0	0
Grade 5	0	0
Diarrhoea	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	32 (13)	26 (12)
Grade 3	2 (1)	2 (1)
Grade 4	0	0
Grade 5	0	2 (1)
Arthralgia	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	30 (13)	19 (8)
Grade 3	2 (1)	1 (<1)
Grade 4	0	0
Grade 5	0	0
Neutropenia	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	10 (4)	13 (6)
Grade 3	11 (5)	50 (22)
Grade 4	16 (7)	66 (29)
Grade 5	0	0
Hypertension	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	14 (6)	9 (4)
Grade 3	15 (6)	11 (5)
Grade 4	0	0
Grade 5	0	0
Fatigue	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	25 (10)	34 (15)
Grade 3	3 (1)	2 (1)
Grade 4	0	0
Grade 5	0	0
Cough	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	27 (11)	23 (10)
Grade 3	0	0
Grade 4	0	0
Grade 5	0	0
Headache	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	26 (11)	17 (7)
Grade 3	0	0
Grade 4	0	0
Grade 5	0	0
Rash	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	26 (11)	38 (17)
Grade 3	0	6 (3)
Grade 4	0	0
Grade 5	0	0
Constipation	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	23 (10)	43 (19)
Grade 3	1 (<1)	0
Grade 4	0	0
Grade 5	0	0
Nausea	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	24 (10)	71 (31)
Grade 3	0	3 (1)
Grade 4	0	0
Grade 5	0	0
Back pain	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	21 (9)	15 (7)
Grade 3	0	1 (<1)
Grade 4	0	0
Grade 5	0	0
Pyrexia	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	17 (7)	52 (23)
Grade 3	0	8 (4)
Grade 4	0	0
Grade 5	0	0
Vomiting	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	17 (7)	30 (13)
Grade 3	0	3 (1)
Grade 4	0	0
Grade 5	0	0
Pneumonia	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	8 (3)	9 (4)
Grade 3	4 (2)	9 (4)
Grade 4	0	0
Grade 5	0	1 (<1)
Anaemia	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	10 (4)	38 (17)
Grade 3	1 (<1)	4 (2)
Grade 4	0	0
Grade 5	0	0
Basal cell carcinoma	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	10 (4)	3 (1)
Grade 3	1 (<1)	0
Grade 4	0	0
Grade 5	0	0
Thrombocytopenia	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	5 (2)	14 (6)
Grade 3	3 (1)	10 (4)
Grade 4	1 (<1)	6 (3)
Grade 5	0	0
Infusion-related reaction^‡	*BRUKINSA (n=240)**	Bendamustine + rituximab (n=227^†)
Grade 1-2	1 (<1)	37 (16)
Grade 3	0	5 (2)
Grade 4	0	1 (<1)
Grade 5	0	0

Grade 1–2 adverse events occurring in ≥10% of patients, or ≥Grade 3 in ≥5% of patients in any group. Patients who had more than one adverse event of the same type were counted once under the highest grade. Adverse events listed occurred during treatment or follow-up, excluding events that occurred after progression. The safety population included all patients who began the assigned treatment. *One patient in the BRUKINSA group did not receive BRUKINSA and is not included in the safety analysis. ^†11 patients did not receive bendamustine + rituximab and are not included in the safety analysis. ^‡Due to amphotericin B infusion. Adapted from Tam CS, et al. Lancet Oncol. 2022.¹

Table 6. SEQUOIA Cohort 1 adverse events of interest.⁶

Patients without del(17p)
Any adverse event of Interest	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	207 (86.3)	206 (90.7)
Grade ≥3	96 (40.0)	156 (68.7)
Anaemia	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	11 (4.6)	44 (19.4)
Grade ≥3	1 (0.4)	4 (1.8)
Arthralgia	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	32 (13.3)	20 (8.8)
Grade ≥3	2 (0.8)	1 (0.4)
Atrial fibrillation	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	8 (3.3)	6 (2.6)
Grade ≥3	1 (0.4)	3 (1.3)
Bleeding	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	108 (45.0)	25 (11.0)
Grade ≥3	9 (3.8)	4 (1.8)
Bruising	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	58 (24.2)	9 (4.0)
Grade ≥3	0	0
Major Bleeding	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	12 (5.0)	4 (1.8)
Grade ≥3	9 (3.8)	4 (1.8)
Minor Bleeding	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	68 (28.3)	15 (6.6)
Grade ≥3	0	0
Petechiae	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	18 (7.5)	0
Grade ≥3	1 (0.4)	0
Diarrhoea	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	33 (13.8)	31 (13.7)
Grade ≥3	2 (0.8)	5 (2.2)
Hypertension	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	34 (14.2)	24 (10.6)
Grade ≥3	15 (6.3)	11 (4.8)
Infections	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	149 (62.1)	127 (55.9)
Grade ≥3	39 (16.3)	43 (18.9)
Myalgia	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	9 (3.8)	3 (1.3)
Grade ≥3	0	0
Neutropenia	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	38 (15.8)	129 (56.8)
Grade ≥3	28 (11.7)	116 (51.1)
Other cancers	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	31 (12.9)	20 (8.8)
Grade ≥3	17 (7.1)	7 (3.1)
Dermatologic other cancers	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	16 (6.7)	10 (4.4)
Grade ≥3	2 (0.8)	2 (0.9)
Thrombocytopenia	BRUKINSA (n=240)	Bendamustine + rituximab (n=227)
Any grade	11 (4.6)	40 (17.6)
Grade ≥3	5 (2.1)	18 (7.9)

Adverse events listed occurred during treatment or follow-up, excluding events that occurred after progression. Patients with multiple events for any term in a grouped analysis were counted once. Safety population included all patients who began the assigned treatment. A subject may be counted in more than one row. Adapted from Tam CS, et al. Lancet Oncol. 2022. Supplementary appendix.⁶

A total of 98% (109/111) of patients experienced an adverse event.⁶

The most common adverse events were upper respiratory tract infection (21%), arthralgia (20%), contusion (20%), diarrhoea (17%), nausea (15%), and constipation (15%).¹

Adverse events, common adverse events, and adverse events of interest are summarised in Tables 7–9.

Table 7. SEQUOIA Cohort 2 adverse events (n, %).^1,6

Any adverse event, n (%)	BRUKINSA (n=111)
Grade 1-2	48 (43)
Grade 3	48 (43)
Grade 4	10 (9)
Grade 5	3 (3)
Serious	BRUKINSA (n=111)
Grade 1-2	7 (6)
Grade 3	34 (31)
Grade 4	1 (1)
Grade 5	3 (3)
All bleeding adverse events*	BRUKINSA (n=111)
Grade 1-2	51 (46)
Grade 3	6 (5)
Grade 4	0
Grade 5	0
All cardiac adverse events*	BRUKINSA (n=111)
Grade 1-2	12 (11)
Grade 3	3 (3)
Grade 4	1 (1)
Grade 5	1 (1)
Dose reduction due to AEs	BRUKINSA (n=111)
Any grade	6 (5)
Discontinuation due to AEs	BRUKINSA (n=111)
Any grade	6 (5)

*Grouped analyses. Adapted from Tam CS, et al. Lancet Oncol. 2022 and Supplementary appendix.^1,6

Table 8. SEQUOIA Cohort 2 common adverse events.¹

Contusion	BRUKINSA (n=111)
Grade 1-2	22 (20)
Grade 3	0
Grade 4	0
Grade 5	0
Upper respiratory tract infection	BRUKINSA (n=111)
Grade 1-2	23 (21)
Grade 3	0
Grade 4	0
Grade 5	0
Diarrhoea	BRUKINSA (n=111)
Grade 1-2	18 (16)
Grade 3	1 (1)
Grade 4	0
Grade 5	0
Arthralgia	BRUKINSA (n=111)
Grade 1-2	21 (19)
Grade 3	1 (1)
Grade 4	0
Grade 5	0
Neutropenia	BRUKINSA (n=111)
Grade 1-2	3 (3)
Grade 3	8 (7)
Grade 4	9 (8)
Grade 5	0
Hypertension	BRUKINSA (n=111)
Grade 1-2	5 (5)
Grade 3	5 (5)
Grade 4	0
Grade 5	0
Fatigue	BRUKINSA (n=111)
Grade 1-2	9 (8)
Grade 3	1 (1)
Grade 4	0
Grade 5	0
Cough	BRUKINSA (n=111)
Grade 1-2	14 (13)
Grade 3	0
Grade 4	0
Grade 5	0
Headache	BRUKINSA (n=111)
Grade 1-2	10 (9)
Grade 3	2 (2)
Grade 4	0
Grade 5	0
Rash	BRUKINSA (n=111)
Grade 1-2	16 (14)
Grade 3	0
Grade 4	0
Grade 5	0
Constipation	BRUKINSA (n=111)
Grade 1-2	17 (15)
Grade 3	0
Grade 4	0
Grade 5	0
Nausea	BRUKINSA (n=111)
Grade 1-2	17 (15)
Grade 3	0
Grade 4	0
Grade 5	0
Back pain	BRUKINSA (n=111)
Grade 1-2	15 (14)
Grade 3	1 (1)
Grade 4	0
Grade 5	0
Pyrexia	BRUKINSA (n=111)
Grade 1-2	7 (6)
Grade 3	1 (1)
Grade 4	0
Grade 5	0
Vomiting	BRUKINSA (n=111)
Grade 1-2	8 (7)
Grade 3	0
Grade 4	0
Grade 5	0
Pneumonia	BRUKINSA (n=111)
Grade 1-2	7 (6)
Grade 3	5 (5)
Grade 4	0
Grade 5	1 (1)
Anaemia	BRUKINSA (n=111)
Grade 1-2	6 (5)
Grade 3	0
Grade 4	0
Grade 5	0
Basal cell carcinoma	BRUKINSA (n=111)
Grade 1-2	12 (11)
Grade 3	0
Grade 4	0
Grade 5	0
Thrombocytopenia	BRUKINSA (n=111)
Grade 1-2	3 (3)
Grade 3	1 (1)
Grade 4	0
Grade 5	0
Infusion-related reaction	BRUKINSA (n=111)
Grade 1-2	0
Grade 3	0
Grade 4	0
Grade 5	0

Grade 1–2 adverse events occurring in ≥10% of patients, or Grade ≥3 in ≥5% of patients in any group. Patients who had more than one adverse event of the same type were counted once under the highest grade. Adverse events listed occurred during treatment or follow-up, excluding events that occurred after progression. The safety population included all patients who began the assigned treatment. Adapted from Tam CS, et al. Lancet Oncol. 2022.¹

Table 9. SEQUOIA Cohort 2 adverse events of interest.⁶

Patients with del(17p)
Any adverse event of interest, n (%)	BRUKINSA (n=111)
Any grade	103 (92.8)
Grade ≥3	46 (414)
Anaemia	BRUKINSA (n=111)
Any grade	6 (5.4)
Grade ≥3	0
Arthralgia	BRUKINSA (n=111)
Any grade	22 (19.8)
Grade ≥3	1 (0.9)
Atrial fibrillation	BRUKINSA (n=111)
Any grade	5 (4.5)
Grade ≥3	4 (3.6)
Bleeding	BRUKINSA (n=111)
Any grade	57 (51.4)
Grade ≥3	6 (5.4)
Bruising	BRUKINSA (n=111)
Any grade	28 (25.2)
Grade ≥3	0
Major bleeding	BRUKINSA (n=111)
Any grade	8 (7.2)
Grade ≥3	6 (5.4)
Minor bleeding	BRUKINSA (n=111)
Any grade	34 (30.6)
Grade ≥3	0
Petechiae	BRUKINSA (n=111)
Any grade	5 (4.5)
Grade ≥3	0
Diarrhoea	BRUKINSA (n=111)
Any grade	19 (17.1)
Grade ≥3	1 (0.9)
Hypertension	BRUKINSA (n=111)
Any grade	12 (10.8)
Grade ≥3	6 (5.4)
Infections	BRUKINSA (n=111)
Any grade	79 (71.2)
Grade ≥3	19 (17.1)
Myalgia	BRUKINSA (n=111)
Any grade	6 (5.4)
Grade ≥3	1 (0.9)
Neutropenia	BRUKINSA (n=111)
Any grade	21 (18.9)
Grade ≥3	18 (16.2)
Other cancers	BRUKINSA (n=111)
Any grade	24 (21.6)
Grade ≥3	7 (6.3)
Dermatologic other cancers	BRUKINSA (n=111)
Any grade	17 (15.3)
Grade ≥3	2 (1.8)
Thrombocytopenia	BRUKINSA (n=111)
Any grade	8 (7.2)
Grade ≥3	1 (0.9)