28.3 Month Follow up

Safety (28.3 Month Follow up)

Most Common AEs
Events of Clinical Interest
Summary of Events Leading to Death

Most Common AEs

AEs with acala were mostly grade 1-2¹

AEs occurring in ≥15% patients, n (%)¹

	Acala-O N=178		Acalabrutinib N=179		O-Clb N=169
	Any	Grade ≥3	Any	Grade ≥3	Any	Grade ≥3
Headache	71 (39.9)	2 (1.1)	66 (36.9)	2 (1.1)	20 (11.8)	0
Diarrhea	69 (38.8)	8 (4.5)	62 (34.6)	1 (0.6)	36 (21.3)	3 (1.8)
Neutropenia	56 (31.5)	53 (29.8)	19 (10.6)	17 (9.5)	76 (45.0)	70 (41.4)
Fatigue	50 (28.1)	3 (1.7)	33 (18.4)	2 (1.1)	29 (17.2)	1 (0.6)
Contusion	42 (23.6)	0	27 (15.1)	0	7 (4.1)	0
Arthralgia	39 (21.9)	2 (1.1)	28 (15.6)	1 (0.6)	8 (4.7)	2 (1.2)
Cough	39 (21.9)	0	33 (18.4)	1 (0.6)	15 (8.9)	0
URTI	38 (21.3)	4 (2.2)	33 (18.4)	0	14 (8.3)	1 (0.6)
Nausea	36 (20.2)	0	40 (22.3)	0	53 (31.4)	0
Dizziness	32 (18.0)	0	21 (11.7)	0	10 (5.9)	0
IRR	24 (13.5)	4 (2.2)	0	0	67 (39.6)	9 (5.3)
Pyrexia	23 (12.9)	0	12 (6.7)	1 (0.6)	35 (20.7)	1 (0.6)

Note: AEs reported are from the treatment-emergent period (first dose through to 30 days after the last dose of study drug or the first date starting a new CLL therapy, whichever is earliest).

Events of Clinical Interest

Events of clinical interest¹

AEs occurring in ≥15% patients, n (%)^1,2

	Acala-O N=178		Acalabrutinib N=179		O=Clb N=169
	Any	Grade ≥3	Any	Grade ≥3	Any	Grade ≥3
Cardiac events	25 (14.0)	8 (4.5)	25 (14.0)	9 (5.0)	13 (7.7)	3 (1.8)
Atrial fibrillation	5 (2.8)	1 (0.6)	6 (3.4)	0	1 (0.6)	0
Atrial flutter	1 (0.6)	0	1 (0.6)	0	0	0
Ventricular tachyarrhythmias	0	0	0	0	0	0
Bleeding	76 (42.7)	3 (1.7)	70 (39.1)	3 (1.7)	20 (11.8)	0
Hypertension	13 (7.3)	5 (2.8)	8 (4.5)	4 (2.2)	6 (3.6)	5 (3.0
Infections	123 (69.1)	37 (20.8)	117 (65.4)	25 (14.0)	74 (43.8)	14 (8.3)
Tumor lysis syndrome	3 (1.7)	2 (1.1)	0	0	15 (8.9)	13 (7.7)
Second primary malignancies, excluding NMSC	10 (5.6)	6 (3.4)	5 (2.8)	2 (1.1)	3 (1.8)	2 (1.2)

Summary of Events Leading to Death

Summary of events leading to death¹

Event, n (%)	Acala-O (n=178)	Acalabrutinib (n=179)	O-Clb (n=169)
Death	8 (4)	12 (7)	15 (9)
Primary cause of death
CLL disease progression	2 (1)	1 (1)	1 (1)
Richter's transformation	0	1 (1)	1 (1)
Other^a	0	3 (2)	0
Unknown^b	2 (1)	1 (1)	2 (1)
Adverse event	4 (2)^c	6 (3)^d	11 (7)
Within 30 days of last dose
Bacterial sepsis	0	0	1 (1)
Bronchopulmonary aspergillosis	0	1 (1)	0
Cardiac arrest	0	0	1 (1)
Goiter	0	1 (1)^d	0
Myositis	0	1 (1)	0
Pneumonia	1 (1)	0	0
Metastases to bone	1 (1)^c	0	0
Sepsis	2 (1)	0	0
Septic shock	0	1 (1)	0

^aOther reasons for death included cerebrovascular accident (n = 1), glioblastoma (n = 1), and respiratory insufficiency (n = 1); ^bFour patients died of unknown causes, and one patient died at home with a possible cause of cardiac arrest; ^cBone metastases were from recurrence of prostate cancer. Death occurred after data cutoff; ^dComplications from surgery for a multinodular goiter led to tracheostomy, cardiopulmonary arrest, shock, and respiratory failure, and the cause of death was reported as “other”.

Abbreviations

Acala = acalabrutinib

;

AE = adverse event

;

Clb = chlorambucil

;

CLL = chronic lymphocytic leukemia

;

IRR = infusion-related reaction

;

n = number

;

NMSC = non-melanoma skin cancer

;

O = obinutuzumab

;

URTI = upper respiratory tract infection

References

1. Sharman JP, Egyed M, Jurczak W et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-nave chronic lymphocytic leukemia (ELEVATE TN): a randomized, controlled phase 3 trial [article and supplementary appendix]. Lancet. 2020;395:1278-91.
2. Sharman JP, Banerji V, Fogliatto LM, Phase 3 Study of Acalabrutinib Combined With Obinutuzumab or Alone vs Obinutuzumab Plus Chlorambucil in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia: Results from ELEVATE-TN [presentation]. Presented at: American Society of Hematology Annual Meeting; December 7-10, 2019; Orlando, FL. Abs 31.

Document ID: 780f9b60-d375-4516-97d6-9ba58f025de4
Last updated: 17-April-2023