Zanubrutinib in Mantle Cell Lymphoma Management: A Comprehensive Review

Figures & data

Figure 1 BTK Inhibitors Mechanism of Action.

Table 1 Dose Modifications for Use with CYP3A Inhibitors or Inducers

Co-Administered Therapy	Recommended Dose Adjustments
Strong CYP3A4 Inhibitor	80 mg once daily Interrupt dose as recommended for adverse reactions
Moderate CYP3A4 Inhibitor	80 mg once daily Interrupt dose as recommended for adverse reactions
Moderate or strong CYP3A4 inducer	Avoid concomitant use

Table 2 Clinical Efficacy Outcomes in MCL

	Phase I (BGB-3111-AU-003) (N=32)	Phase II Study (BGB-3111-206) (N=86)
ORR, %	84	84
CRR, %	25	59
DOR (mos), median	18.5	19.5
PFS (mos), median	21.1	22.1

Abbreviations: ORR, overall response rate; CRR, complete response rate; DOR, duration of response; PFS, progression-free survival; NE, not estimable; mos, months.

Table 3 Zanubrutinib Adverse Events

Adverse Events	All Grades, n (%)	Grade ≥3, n (%)
Patients with at least one adverse event	83 (96.5)	34 (41.9)
Hematologic events
Neutropenia	42 (48.8)	17 (19.8)
Leukopenia	30 (34.9)	6 (7.0)
Thrombocytopenia	28 (32.6)	4 (4.7)
Anemia	13 (15.1)	5 (5.8)
Nonhematologic events
Upper respiratory tract infection	30 (34.9)	0
Rash	29 (33.7)	0
Hypokalemia	14 (16.3)	1 (1.2)
Diarrhea	13 (15.1)	0
Hypertension	13 (15.1)	3 (3.5)
Alanine aminotransferase increased	12 (14.0)	1 (1.2)
Lung infection	11 (12.8)	8 (9.3)

Table 4 Zanubrutinib Dose Modification Based on AEs

Adverse Event	Adverse Reaction Occurrence	Dose Modification
Grade 3 or higher non-hematological toxicities Grade 3 febrile neutropenia Grade 3 thrombocytopenia with significant bleeding Grade 4 neutropenia (lasting more than 10 consecutive days) Grade 4 thrombocytopenia (lasting more than 10 consecutive days)	First	Hold zanubrutinib Once toxicity has resolved to recovery to Grade 1 or lower or baseline: Resume at 160 mg twice daily or 320 mg once daily
	Second	Hold zanubrutinib Once toxicity has resolved to recovery to Grade 1 or lower or baseline: Resume at 80 mg twice daily or 160 mg once daily
	Third	Hold zanubrutinib Once toxicity has resolved to recovery to Grade 1 or lower or baseline: Resume at 80 mg once daily
	Fourth	Discontinue zanubrutinib
Atrial fibrillation or atrial flutter		Manage as clinically indicated.
Intracranial hemorrhage (any grade)		Discontinue zanubrutinib

Table 5 Ongoing Studies of Zanubrutinib in MCL

Study Design	Arm 1	Arm 2	Key Outcomes	Key Inclusion Criteria	Clinical.gov Identifier
Phase II	Zanubrutinib-based induction followed by autologous stem cell transplant	None	Minimal residual disease negativity rate, PFS, OS	Newly diagnosed MCL	NCT04736914
Phase II	Zanubrutinib plus rituximab	None	ORR, PFS, OS	Newly diagnosed MCL	NCT05504603
Phase III	Zanubrutinib plus rituximab	Bendamustine plus rituximab	PFS, ORR, OS	Newly diagnosed MCL	NCT04002297
Phase I/II	Zanubrutinib and Tafasitamab	None	Dose expansion and dose-limited toxicity, ORR	Phase I: Relapsed MCL Phase II: Untreated MCL	NCT06029309