J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://jh.elmerpub.com

Original Article

Volume 14, Number 6, December 2025, pages 297-306

Efficacy and Safety of Orelabrutinib for Previously Treated Marginal Zone Lymphoma

↓ Figure 1. Comparison of CR (30.00% vs. 53.3%), PR (50.00% vs. 33.33%), SD (10.00% vs. 6.66%), and PD (10.00% vs. 6.66%) between the orelabrutinib and control groups (P > 0.05). CR: complete response; PD: progressive disease; PR: partial response; SD: stable disease.

↓ Figure 2. (a) Overall EFS of the two groups (P = 0.86). (b) EFS of patients after R/R-CT treatment (P = 0.75). Shaded bands denote 95% confidence intervals, and no significant statistical differences were observed in either case. EFS: event-free survival; Ore: orelabrutinib; R/BR: rituximab/bendamustine plus rituximab; R/R-CT: rituximab/rituximab-based chemotherapy.

↓ Figure 3. The numbers of adverse events in the two groups. 3/4 TRAE: grade 3/4 treatment-related adverse event. PSM: propensity score matching; R/BR: rituximab/bendamustine plus rituximab.

↓ **Table 1.** Before PSM
Characteristic	Orelabrutinib (N = 30)	R/BR (N = 81)	P
ECOG: Eastern Cooperative Oncology Group; EMZL: extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue; NMZL: nodal marginal zone lymphoma; PSM: propensity score matching; R/BR: rituximab or rituximab plus bendamustine; R/R-CT: rituximab/rituximab-based chemotherapy; SMZL: splenic marginal zone lymphoma.
Male, n (%)	19 (63.33)	46 (56.79)	0.66
Age (years)			0.18
Mean (standard deviation)	61.00 (10.03)	57.64 (10.57)
Median (range)	60 (35 - 80)	59 (30 - 78)
After R/R-CT, n (%)	17 (56.66)	25 (30.86)	0.01
Subtype diagnosis, n (%)			0.69
EMZL	15 (50.00)	48 (59.25)
NMZL	9 (30.00)	21 (25.92)
SMZL	6 (20.00)	12 (14.81)
Stage III/IV, n (%)	24 (80.00)	57 (70.37)	0.34
Prognosis, n (%)			0.47
Low-risk	5 (16.66)	23 (28.39)
Middle-risk	15 (50.00)	36 (44.44)
High-risk	10 (33.33)	22 (27.16)
Ki-67, n (%)			0.22
< 15%	4 (13.33)	24 (29.62)
15% ≤ Ki-67 < 30%	19 (63.33)	40 (49.38)
≥ 30%	7 (23.33)	17 (20.98)
Bone marrow assessment, n (%)			1.00
Positive	7 (23.33)	18 (22.22)
ECOG ≥ 3, n (%)	5 (16.66)	9 (11.11)	0.30

↓ Table 1. Before PSM

Characteristic

Orelabrutinib (N = 30)

R/BR (N = 81)

ECOG: Eastern Cooperative Oncology Group; EMZL: extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue; NMZL: nodal marginal zone lymphoma; PSM: propensity score matching; R/BR: rituximab or rituximab plus bendamustine; R/R-CT: rituximab/rituximab-based chemotherapy; SMZL: splenic marginal zone lymphoma.

Male, n (%)

19 (63.33)

46 (56.79)

0.66

Age (years)

0.18

Mean (standard deviation)

61.00 (10.03)

57.64 (10.57)

Median (range)

60 (35 - 80)

59 (30 - 78)

After R/R-CT, n (%)

17 (56.66)

25 (30.86)

0.01

Subtype diagnosis, n (%)

0.69

EMZL

15 (50.00)

48 (59.25)

NMZL

9 (30.00)

21 (25.92)

SMZL

6 (20.00)

12 (14.81)

Stage III/IV, n (%)

24 (80.00)

57 (70.37)

0.34

Prognosis, n (%)

0.47

Low-risk

5 (16.66)

23 (28.39)

Middle-risk

15 (50.00)

36 (44.44)

High-risk

10 (33.33)

22 (27.16)

Ki-67, n (%)

0.22

< 15%

4 (13.33)

24 (29.62)

15% ≤ Ki-67 < 30%

19 (63.33)

40 (49.38)

≥ 30%

7 (23.33)

17 (20.98)

Bone marrow assessment, n (%)

1.00

Positive

7 (23.33)

18 (22.22)

ECOG ≥ 3, n (%)

5 (16.66)

9 (11.11)

0.30

↓ **Table 2.** After PSM
Characteristic	Orelabrutinib (N = 30)	R/BR (N = 30)	P	SMD
ECOG: Eastern Cooperative Oncology Group; EMZL: extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue; NMZL: nodal marginal zone lymphoma; PSM: propensity score matching; R/BR: rituximab or rituximab plus bendamustine; R/R-CT: rituximab/rituximab-based chemotherapy; SMZL: splenic marginal zone lymphoma; SMD: standardized mean difference.
Male, n (%)	19 (63.33)	18 (60.00)	1.00	0.06
Age (years)			0.73	0.08
Mean (standard deviation)	61.03 (10.07)	60.23 (9.31)
Median (range)	60 (35 - 80)	59 (40 - 78)
After R/R-CT, n (%)	17 (56.66)	17 (56.66)	1.00	< 0.01
Relapsed	13 (43.33)	15 (50.00)
Refractory	4 (13.33)	2 (6.66)
Subtype diagnosis, n (%)			1.00	0.06
EMZL	15 (50.00)	15 (50.00)
NMZL	9 (30.00)	10 (33.33)
SMZL	6 (20.00)	5 (16.66)
Stage III/IV, n (%)	24 (80.00)	25 (83.33)	1.00	0.08
Prognosis, n (%)			0.84	0.12
Low-risk	5 (16.66)	7 (26.66)
Middle-risk	15 (50.00)	13 (43.33)
High-risk	10 (33.33)	10 (30.00)
Ki-67, n (%)			0.87	0.10
< 15%	4 (13.33)	5 (16.66)
15% ≤ Ki-67 < 30%	19 (63.33)	17 (56.6)
≥ 30%	7 (23.33)	8 (26.66)
Bone marrow assessment, n (%)
Positive	7 (23.33)	9 (30.00)	0.77	0.14
ECOG ≥ 3, n (%)	5 (16.66)	3 (10.00)	0.70	0.10

↓ Table 2. After PSM

Characteristic

Orelabrutinib (N = 30)

R/BR (N = 30)

SMD

Male, n (%)

19 (63.33)

18 (60.00)

1.00

0.06

Age (years)

0.73

0.08

Mean (standard deviation)

61.03 (10.07)

60.23 (9.31)

Median (range)

60 (35 - 80)

59 (40 - 78)

After R/R-CT, n (%)

17 (56.66)

1.00

< 0.01

Relapsed

13 (43.33)

15 (50.00)

Refractory

4 (13.33)

2 (6.66)

Subtype diagnosis, n (%)

1.00

0.06

EMZL

15 (50.00)

NMZL

9 (30.00)

10 (33.33)

SMZL

6 (20.00)

5 (16.66)

Stage III/IV, n (%)

24 (80.00)

25 (83.33)

1.00

0.08

Prognosis, n (%)

0.84

0.12

Low-risk

5 (16.66)

7 (26.66)

Middle-risk

15 (50.00)

13 (43.33)

High-risk

10 (33.33)

10 (30.00)

Ki-67, n (%)

0.87

0.10

< 15%

4 (13.33)

5 (16.66)

15% ≤ Ki-67 < 30%

19 (63.33)

17 (56.6)

≥ 30%

7 (23.33)

8 (26.66)

Bone marrow assessment, n (%)

Positive

7 (23.33)

9 (30.00)

0.77

0.14

ECOG ≥ 3, n (%)

5 (16.66)

3 (10.00)

0.70

0.10

↓ **Table 3.** Comparison of DCR, ORR, CR, and PR Between Relapsed/Refractory Patients After R/R-CT in the Two Groups (P > 0.05)
	Ore (N = 17)	BR (N = 17)	P
BR: rituximab plus bendamustine; CR: complete response; DCR: disease control rate; EMZL: extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue; NMZL: nodal marginal zone lymphoma; Ore: orelabrutinib; ORR: overall response rate; PR: partial response; R/R-CT: rituximab/rituximab-based chemotherapy; SMZL: splenic marginal zone lymphoma.
DCR, n (%)	14 (82.35	15 (88.23)	1.00
ORR, n (%)	11 (64.70)	13 (76.47)	0.70
CR, n (%)	3 (17.64)	5 (29.41)	0.68
EMZL	2 (11.76)	3 (17.64)	1.00
NMZL	1 (5.88)	2 (11.76)	1.00
SMZL	0	0	-
PR, n (%)	8 (47.05)	8 (47.05)	1.00
EMZL	4 (23.52)	4 (23.52)	1.00
NMZL	3 (17.64)	2 (11.76)	1.00
SMZL	1 (5.88)	2 (11.76)	0.48

↓ Table 3. Comparison of DCR, ORR, CR, and PR Between Relapsed/Refractory Patients After R/R-CT in the Two Groups (P > 0.05)

Ore (N = 17)

BR (N = 17)

BR: rituximab plus bendamustine; CR: complete response; DCR: disease control rate; EMZL: extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue; NMZL: nodal marginal zone lymphoma; Ore: orelabrutinib; ORR: overall response rate; PR: partial response; R/R-CT: rituximab/rituximab-based chemotherapy; SMZL: splenic marginal zone lymphoma.

DCR, n (%)

14 (82.35

15 (88.23)

1.00

ORR, n (%)

11 (64.70)

13 (76.47)

0.70

CR, n (%)

3 (17.64)

5 (29.41)

0.68

EMZL

2 (11.76)

3 (17.64)

1.00

NMZL

1 (5.88)

2 (11.76)

1.00

SMZL

PR, n (%)

8 (47.05)

1.00

EMZL

4 (23.52)

1.00

NMZL

3 (17.64)

2 (11.76)

1.00

SMZL

1 (5.88)

2 (11.76)

0.48

↓ **Table 4.** TRAEs of Orelabrutinib Group
TRAEs	All grades	Grade ≥ 3
TRAE: treatment-related adverse event.
Hematologic adverse events, n (%)
Thrombocytopenia	8 (26.66%)	2 (6.66)
Neutropenia	6 (20.00%)	1 (3.33)
Anemia	4 (13.33%)	-
Lymphopenia	3 (10.00%)	-
Other TRAEs, n (%)
Respiratory tract infection	3 (10.00%)	-
Rash	5 (16.66%)	-
Hematuria	2 (6.66)	-
Hypertension and arrhythmias	-	-
Second tumor	-	-

↓ Table 4. TRAEs of Orelabrutinib Group

TRAEs

All grades

Grade ≥ 3

TRAE: treatment-related adverse event.

Hematologic adverse events, n (%)

Thrombocytopenia

8 (26.66%)

2 (6.66)

Neutropenia

6 (20.00%)

1 (3.33)

Anemia

4 (13.33%)

Lymphopenia

3 (10.00%)

Other TRAEs, n (%)

Respiratory tract infection

3 (10.00%)

Rash

5 (16.66%)

Hematuria

2 (6.66)

Hypertension and arrhythmias

Second tumor