Table 4.

Summary of zanubrutinib adverse events of interest by category.

AEI	EAIR a		All patients with Gr ⩾ 3 event, n (%)
	All-grade	Grade ⩾ 3
Infections	9.6	1.4	214 (27)
Opportunistic infections	0.1	0.1	15 (2)
Hemorrhage b	4.8	0.2	28 (4)
Major hemorrhage	0.2	0.2	28 (4)
Neutropenia c	2.1	1.2	183 (23)
Thrombocytopenia d	1.1	0.3	61 (8)
Anemia e	0.8	0.04	63 (8)
Second primary malignancies f	0.6	0.2	40 (5)
Skin cancers	0.4	0.1	13 (2)
Hypertension	0.6	0.2	41 (5)
Atrial fibrillation and flutter	0.1	0.03	6 (1)
Tumor lysis syndrome g	0.02	0.02	3 (0.4)

AEI, adverse event of interest; EAIR, exposure-adjusted incidence rate; Gr, grade; PT, preferred term.

^aEAIRs calculated as the first occurrence of each adverse event of interest per 100 person-months of zanubrutinib exposure.

^bIncludes major hemorrhage.

^cIncludes clinical adverse events reported under PTs neutropenia (n = 97), neutrophil count decreased (n = 178), febrile neutropenia (n = 14), and neutropenic sepsis (n = 1).

^dIncludes clinical adverse events reported under the PTs thrombocytopenia (n = 58) and platelet count decreased (n = 97).

^eIncludes clinical adverse events reported under the PTs anemia (n = 125) and hemoglobin decreased (n = 6).

^fInclusive of skin cancers.

^gTwo cases of tumor lysis syndrome occurred > 30 days after discontinuation of zanubrutinib for disease progression; both were assessed as grade ⩾ 3 and serious. In one patient, the event occurred in association with venetoclax exposure, a known precipitant of tumor lysis syndrome. A third patient experienced an event with onset 9 days after discontinuation of zanubrutinib for progression of mantle cell lymphoma on study day 150, which was unresponsive to medical management. The patient died 3 days after onset from complications of acute kidney injury.