Updated Real-World Outcomes with Brentuximab Vedotin in Chinese Lymphoma Patients: A Multicenter, Retrospective Study

Abstract

Purpose

Brentuximab vedotin (BV) has been increasingly used in the treatment of CD30-positive lymphomas since its approval in China in 2020. We aimed to evaluate the effectiveness and safety of BV-based regimens in a real-world setting with a larger cohort and longer follow-up period from a 2022 study.

Patients and Methods

This multi-center, retrospective study included patients diagnosed with lymphoma treated with BV-based regimens between August 2020 and April 2025 at three real-world centers in central China.

Results

A total of 252 CD30-positive lymphoma patients were collected: 44.8% were cHL, 27.4% were sALCL and 27.8% were other types of lymphoma, who accomplished a median of 4 cycles of BV-based therapy. Effectiveness analysis was performed on 234 patients, revealing an overall response rate (ORR) of 67.1% and a complete response (CR) rate of 39.7%. After a median follow-up of 17.6 months (range: 0.1–55.6 months), the 1-year, 2-year and 3-year progression-free survival (PFS) rates were 72.7%, 69.4% and 69.4%, respectively, while the 1-year, 2-year and 3-year overall survival (OS) rates were 87.0%, 83.7% and 83.7%, respectively. First-line BV-based treatment yielded significantly better CR rates, although no significant survival advantage was observed after adjustment for confounding factors. The overall incidence of adverse events (AEs) of any grade was 85.7%, with the most frequently reported AEs being anemia, leukopenia, and infections. A total of 44 patients underwent stem cell transplantation (SCT), with 31 patients receiving BV-based bridge therapy and 10 patients receiving BV as consolidation therapy following SCT.

Conclusion

Our findings further solidify the role of BV as an efficacious and generally well-tolerated treatment in CD30-positive lymphomas. Its clinical activity was observed across first-line, bridging, and post-SCT settings. However, given the heterogeneous lymphoma subtypes and treatment settings included in this real-world cohort, further prospective studies are warranted.

Introduction

Brentuximab vedotin (BV), a novel anti-CD30 antibody‒drug conjugate (ADC), was approved in 2020 for the treatment of relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL), systemic anaplastic large cell lymphoma (sALCL), and previously treated primary cutaneous anaplastic large cell lymphoma (pcACLC) or mycosis fungoides (MF) in China. In addition to cHL, sALCL, and primary cutaneous T-cell lymphoma (PC-TCL), various other T-cell and B-cell lymphomas also express CD30 to differing extents, thereby benefiting from BV-based therapies.

In recent years, the inclusion of BV in national healthcare systems and the growing body of real-world evidence in China have contributed to its expanded use in clinical practice. Moreover, BV has been recommended for the first-line treatment of cHL and CD30+ peripheral T-cell lymphoma (PTCL), including sALCL, nodal T-follicular helper cell lymphoma (nTFHL), peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), and PC-TCL, according to the Chinese Society of Clinical Oncology (CSCO) guidelines, integrating BV into frontline treatment regimens. For patients with R/R cHL and PTCL, BV-based bridge therapy is recommended for those eligible for stem cell transplantation (SCT), while high-risk cHL patients may be considered for BV as a consolidation treatment following SCT.

Initial results from a multi-center study conducted across eight centers in Henan Province, China, published in 2023, demonstrated that BV is safe and efficacious for treating Chinese lymphoma patients, with a median follow-up of 11 months and a limited cohort size. Building on this, we performed a multi-center, real-world study to provide updated data following an extended follow-up period and a larger patient cohort.1 The aim was to further unravel the real-world application, effectiveness, and safety of BV-based therapy in a real-life context in China.

Patients and Methods

Study Design and Patient Population

This multi-center, real-world study included all patients diagnosed with lymphoma through pathology who received at least one cycle of BV monotherapy or BV combination therapy between August 2020 and April 2025 at three centers in Henan Province in China. Clinical data, including age, sex, hospital, lymphoma subtypes, Ann Arbor stage, EBV infection status, bone marrow involvement, central nervous system (CNS) involvement, disease status, number of BV cycles, treatment response, survival outcomes, adverse events, and others, were extracted from patient medical records across the three centers: the First Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital, and Henan Provincial People’s Hospital. The study was conducted in accordance with the Declaration of Helsinki at the First Affiliated Hospital of Zhengzhou University and was approved by the ethics committees of all participating centers. For patients under 18 years of age, written informed consent was obtained from their parents or legal guardians prior to treatment and data collection.

Patients with incomplete medical records or missing follow-up data were excluded from the analysis. EBV infection was uniformly assessed by Epstein–Barr virus–encoded RNA (EBER) in situ hybridization on tumor tissue samples. Treatment response assessments were performed according to the 2014 Lugano classification criteria using computed tomography (CT) and/or positron emission tomography-computed tomography (PET-CT). Imaging evaluations were conducted after every 2–4 treatment cycles or when disease progression was clinically suspected. Responses were categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The overall response rate (ORR) was defined as the percentage of patients achieving CR or PR. To ensure consistency, each patient’s response was independently reviewed by two hematologists at each participating center, and discrepancies were resolved by consensus. Safety evaluations were conducted according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE version 4.0).

Follow-Up and Statistical Analysis

Follow-up was extended via telephone interviews or further consultation until April 2025. Overall survival (OS) was calculated from the initiation of BV-based therapy to death or the last observation, regardless of the cause of death, while progression-free survival (PFS) was defined as the time from the initiation of BV-based therapy to the first relapse, progression, death, or last follow-up. SPSS software version 26.0 and Python 3.13.0 were applied for statistical analysis in our study. Normally descriptive statistics were presented as percentages and medians. Treatment effectiveness was compared using the chi-squared test. Kaplan‒Meier survival analyses were conducted to express PFS and OS. The Log rank test was performed to compare the differences between survival curves of each cohort. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. A p value of <0.05 was considered statistically significant.

Results

Baseline Patient Characteristics

Between August 2020 and April 2025, a total of 252 patients from three centers in the central regions of China were enrolled in this study. Among them, 44.8% (n=113) had cHL, 27.4% (n=69) had sALCL, and 27.8% (n=70) had other types of lymphoma, including TFHL, PTCL-NOS, diffuse large B-cell lymphoma (DLBCL), extranodal NK/T-cell lymphoma (ENKTCL), and CTCL. The median age of the patients was 42.0 years (range: 2.0–86.0), with 56 patients (22.2%) being over 60 years of age (Table 1). A majority of patients (82.9%) were diagnosed at advanced stages (stage III–IV) when they began BV treatment, and 57.1% were relapsed/refractory (R/R) cases. Among the 50 patients with EBV-positive lymphomas, 21 had cHL, 17 had nTFHL, 4 had DLBCL, 3 had PTCL-NOS, 2 had sALCL, and 1 had mycosis fungoides (MF). 32 patients (12.7%) developed bone marrow involvement, and 8 patients (3.9%) exhibited central nervous system involvement. On average, patients received a median of 4 cycles of BV-based therapy, with 42.9% (n=108) receiving BV as first-line treatment.

Table 1.

Baseline Characteristics of 252 Patients

Characteristics		N (%)
Patients		252 (100.0%)
Age, years	Median age (range)	42 (2–86)
	<18 years	31 (12.3%)
	18–60 years	165 (65.5%)
	>60 years	56 (22.2%)
Sex	Male Female	134 (53.2%) 118 (46.8%)
Center	The First Affiliated Hospital of Zhengzhou University	95 (37.7%)
	Henan Cancer Hospital	80 (31.7%)
	Henan Provincial People’s Hospital	77 (30.6%)
Lymphoma type	cHL	113 (44.8%)
	sALCL	69 (27.4%)
	nTFHL	24 (9.5%)
	PTCL-NOS	21 (8.3%)
	DLBCL	13 (5.2%)
	ENKTCL	3 (1.2%)
	PC-TCL	9 (3.6%)
Stage	I	6 (2.4%)
	II	37 (14.7%)
	III	60 (23.8%)
	IV	149 (59.1%)
EBV	Positive	50 (19.8%)
	Negative	170 (67.5%)
	Unknown	32 (12.7%)
Bone marrow involvement	Yes	32 (12.7%)
	No	220 (87.3%)
Central involvement	Yes	8 (3.2%)
	No	244 (96.8%)
Disease status prior to BV	Untreated	108 (42.9%)
	Relapsed	64 (25.4%)
	Refractory	80 (31.7%)
ASCT	Yes	44 (17.5%)
	No	208 (82.5%)
BV cycles, n	Median	4
	Range	1–21
BV-based treatment	First-line	108 (42.9%)
	Second-line or post-line	144 (57.1%)

Abbreviations: cHL, classical Hodgkin lymphoma; sALCL, systemic anaplastic large cell lymphoma; nTFHL, nodal T-follicular helper cell lymphoma; PTCL-NOS, peripheral T-cell lymphoma-not otherwise specified; DLBCL, diffuse large B-cell lymphoma; ENKTCL, extranodal NK/T-cell lymphoma; PC-TCL, primary cutaneous T-cell lymphoma.

Treatment Response by Lymphoma Subtypes

A total of 234 patients underwent effectiveness evaluation, with an ORR of 67.1% and a CR rate of 39.7% (Table 2). In the cHL cohort, the ORR was 75.2%, and the CR rate was 49.5%. In the sALCL cohort, the ORR was 68.8%, with 45.3% of patients achieving CR. Among patients with other types of lymphoma, the ORR was 52.3%, and the CR rate was 18.5%. Statistically significant differences were observed in both the ORR and CR rate across the three groups (p = 0.008 and p = 0.000, respectively). Patients with cHL and sALCL demonstrated significantly better ORR (p = 0.000 and p = 0.000) and CR rate (p = 0.000 and p = 0.001) compared to those with other types of lymphoma. Descriptive treatment outcomes for different subtypes beyond cHL and sALCL are summarized in Table S1.

Table 2.

Response to BV-Based Treatment in Different Types of Lymphoma

Effectiveness, n(%)	cHL, n=105	sALCL, n=64	Other typesa, n=65	Total, n=234
ORR	79(75.2)	44(68.8)	34(52.3)	157(67.1)
CR	52(49.5)	29(45.3)	12(18.5)	93(39.7)
PR	27(25.7)	15(23.4)	22(33.8)	64(27.4)
SD	12(11.4)	5(7.8)	9(13.8)	26(11.1)
PD	14(13.3)	15(23.4)	22(33.8)	51(21.8)

Notes: ^aOther types include: nodal T-follicular helper cell lymphoma, peripheral T-cell lymphoma-not otherwise specified, diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, and primary cutaneous T-cell lymphoma.

Abbreviations: cHL, classical Hodgkin lymphoma; sALCL, systemic anaplastic large cell lymphoma; ORR, overall response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.

The median duration of follow-up was 17.6 months (range: 0.1–55.6). The 1-year, 2-year and 3-year PFS rates were 72.7%, 69.4% and 69.4%, respectively, while the 1-year, 2-year and 3-year OS rates were 87.0%, 83.7% and 83.7%, respectively (Figure 1).

Figure 1.

Kaplan-Meier survival curves of 234 patients. (A) The progression-free survival curve among 234 patients. (B) The overall survival curve among 234 patients.

In the cHL cohort, the 1-year, 2-year and 3-year PFS rates were 84.4%, 82.6% and 82.6%, respectively, while in the sALCL cohort, the rates were all 68.3%. In patients with other types of lymphoma, the 1-year, 2-year and 3-year PFS rates were 57.9%, 47.2% and 47.2%, respectively. The 1-year OS rate was 95.7% in cHL, 89.8% in sALCL, and 70.4% in patients with other lymphoma types; the 2-year and 3-year OS rates were 95.7%, 85.4%, and 63.3%, respectively, in these three cohorts. The median OS and median PFS were not reached (Figure 2). PFS was significantly better in patients with cHL and sALCL compared to those with other lymphoma types (p = 0.000 and p = 0.041). Additionally, patients in the cHL and sALCL cohort had significantly prolonged OS compared to those with other lymphoma types (p = 0.000 and p = 0.006). Compared with sALCL, cHL patients also achieved improved PFS and OS (p= 0.01 and p= 0.027).

Figure 2.

Kaplan-Meier survival curves among patients with different lymphoma subtypes. (A) The progression-free survival curve among 234 patients with cHL, sALCL and other types of lymphoma. (B) The overall survival curve among 234 patients with cHL, sALCL and other types of lymphoma.

Treatment Response by Line of BV-Based Therapy

Among 108 patients who received BV as first-line treatment, the effectiveness was evaluated in 101 patients (Table 3). The ORR was 73.3%, with nearly half of the patients reached a CR (n=50, 49.5%). Among patients with R/R diseases before BV-based therapy, including 64 with relapsed diseases and 80 with refractory diseases, 133 were evaluable for response, and the ORR reached 62.4%. No significant differences in ORR was observed between these two groups (p= 0.08). However, patients who received BV as first-line therapy demonstrated a significantly higher CR rate compared with those with R/R disease (p= 0.008).

Table 3.

Response to BV-Based Treatment in Different Disease Status of Lymphoma

Effectiveness, n(%)	Untreated (First-line), n=101	R/R (Second-line or later), n=133
ORR	74(73.3)	83(62.4)
CR	50(49.5)	43(32.3)
PR	24(22.9)	40(30.1)
SD	8(7.6)	18(13.5)
PD	19(18.1)	32(24.1)

Abbreviations: R/R, relapsed/refractory; ORR, overall response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.

After a median follow-up of 16.0 months (range: 0.8–45.4), the 1-year, 2-year and 3-year PFS rates among patients receiving BV-based first-line treatment regimens were all 76.0%. The 1-year, 2-year and 3-yearOS rates were 91.4%, 87.5%and 87.5%, respectively (Figure 3). For patients in second or later-lines of BV-based therapy, the 1-year, 2-year and 3-year PFS rates were 70.5% and 65.3% and 65.3%, respectively, while the 1-year, 2-year and 3-year OS rates were 84.1% and 81.1% and 81.1%, respectively. No significant differences in PFS or OS were observed between these two groups (p = 0.241 and p = 0.187, respectively; Figure S1).

Figure 3.

Kaplan-Meier survival curves of 101 patients who received BV as first-line therapy. (A) The progression-free survival curve among 101 patients. (B) The overall survival curve among 101 patients.

Overall Safety

Adverse events (AEs) associated with BV-based treatment observed in our study are listed in Table 4. Overall, BV was well tolerated, with 26 patients (10.3%) of the 252 enrolled having no reported AEs, including those receiving BV monotherapy and BV combination therapy. The most commonly reported AEs of any grade were anemia (n=104, 41.3%), leukopenia (n=98, 38.9%), and infection (n=74, 29.4%). The most frequent AEs of grade 3 or higher were leukopenia (n=45, 17.9%), infection (n=29, 11.5%), and thrombocytopenia (n=13, 5.2%). Peripheral sensory neuropathy of any grade was reported in 11 patients, with 3 cases classified as grade 3 or higher. Importantly, no patients required dose reduction or treatment discontinuation due to adverse events.

Table 4.

Adverse Events- During BV-Based Treatment

AEs Reported	Total Number of Events	Grade≥3 Number of Events
Anemia	104	9
Leukopenia	98	45
Thrombocytopenia	48	13
Infection	74	29
Abnormal liver function	30	4
Hypoproteinemia	26	0
Hypokalemia	17	1
Fever	15	0
Nausea	13	0
Peripheral neuropathy	11	3
Rash	7	0
Hypothyroidism	5	0
Hyperuricemia	4	0
Intestinal obstruction	4	0
Diarrhea	2	0

Abbreviation: AEs, adverse events.

The mortality rate among older patients (≥60 years) was 37.5%. In this group, BV toxicity was generally manageable, with an overall AE incidence of 91.1%. While hematologic disorders and infections occurred more frequently in older patients, no AE-related deaths were observed in our study. All AEs and those of grade ≥3 occurring in elderly patients are listed in Table S2.

BV Monotherapy and Transplantation

Among the 252 patients included in this study, 42 received BV monotherapy during their treatment course. Specifically, 19 patients received BV monotherapy for relapsed or refractory disease, 14 for maintenance therapy, 1 as pre-transplant bridging therapy, 7 as post-transplant consolidation, and 1 received BV both as pre- and post-transplant treatment. Among these 42 patients, 18 were treated exclusively with BV monotherapy, while the remaining patients received both BV monotherapy and BV-based combination regimens at different treatment stages.

Among the 44 patients who underwent SCT in our study, 27 received BV prior to SCT, 9 received BV after SCT, and 8 patients received BV both pre- and post-SCT. A total of 31 patients were treated with BV as a bridge therapy to SCT, while 10 high-risk patients received BV as consolidation therapy after SCT, and 7 patients received BV after SCT failure (Figure 4). Lymphoma subtypes, best responses, BV-based treatment regimens, and survival outcomes are detailed in Table S3. Specifically, among the 31 patients who received BV as bridging therapy before SCT, 18 achieved CR and 13 achieved PR. These data indicate that BV is a promising bridge therapy for patients, enabling sufficient responses prior to SCT and yielding favorable survival outcomes.

Figure 4.

Disposition of BV users who ever underwent SCT.

Analysis of Prognostic Factors

Univariate and multivariate Cox regression analyses were performed to explore the underlying prognostic factors among 234 patients and to minimize potential confounding inherent to real-world data. Age (<18 years, 18–60 years, and >60 years), Ann Arbor stage (early and advanced), lymphoma subtype (cHL, sALCL, and others), bone marrow involvement (yes and no), CNS involvement (yes and no), and line of BV-based therapy (first-line and second- or later-line) were included in the univariate Cox regression analysis. It is demonstrated that age >60 years and lymphoma subtypes (sALCL and others) were significantly associated with inferior PFS (Table 5). For OS, univariate analysis identified age >60 years, lymphoma subtype, bone marrow involvement, and CNS involvement as significant adverse prognostic factors (Table 6). Variables with statistical significance in the univariate analysis were subsequently included in the multivariate model, together with both Ann Arbor stage, an important clinical prognostic factor, and BV-based treatment line, which is further validated in our study. In multivariate analysis, age >60 years and lymphoma subtype (sALCL and others) were identified as independent risk factors for inferior PFS, while age >60 years, bone marrow involvement, CNS involvement, and other types of lymphoma were independent risk factors for dismal OS. Nevertheless, frontline use of BV-based treatment was not an independent prognostic factor with prolonged PFS or OS after adjustment for confounding variables.

Table 5.

Univariate and Multivariate COX Analysis in 234 Patients (PFS)

Variables	Univariate Analysis (PFS)		Multivariate Analysis (PFS)
	HR (95% CI)	P value	HR (95% CI)	P value
Age
<18	0.57(0.20–1.59)	0.279	0.65(0.23–1.86)	0.425
18–60	Ref		Ref
>60	2.50(1.51–4.15)	0.000	1.93(1.12–3.34)	0.019
Ann Arbor Stage
Early (I-II)	Ref		Ref
Advanced (III-IV)	1.20(0.63–2.29)	0.591	1.02(0.53–1.98)	0.948
Lymphoma subtypes
cHL	Ref		Ref
sALCL	2.26(1.17–4.37)	0.015	2.50(1.28–4.86)	0.007
othersa	4.06(2.21–7.46)	0.000	3.17(1.67–6.04)	0.000
Bone marrow involvement
Yes	1.67(0.89–3.12)	0.111
No	Ref
CNS involvement
Yes	1.51(0.47–4.84)	0.485
No	Ref
Line of BV-based therapy
First-line	0.74(0.44–1.23)	0.244	0.74(0.44–1.26)	0.267
Second- or later- line	Ref		Ref

Notes: ^aOthers include: nodal T-follicular helper cell lymphoma, peripheral T-cell lymphoma-not otherwise specified, diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, and primary cutaneous T-cell lymphoma.

Abbreviations: PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; cHL, classical Hodgkin lymphoma; sALCL, systemic anaplastic large cell lymphoma; ORR, overall response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; Ref, reference; CNS, central nervous system.

Table 6.

Univariate and Multivariate COX Analysis in 234 Patients (OS)

Variables	Univariate Analysis (OS)		Multivariate Analysis (OS)
	HR (95% CI)	P value	HR (95% CI)	P value
Age
<18	0.85(0.19–3.78)	0.835	1.11(0.23–5.29)	0.893
18–60	Ref		Ref
>60	5.07(2.50–10.30)	0.000	5.81(2.53–13.33)	0.000
Ann Arbor Stage
Early (I-II)	Ref		Ref
Advanced (III-IV)	0.86(0.38–1.99)	0.731	0.40(0.16–1.02)	0.055
Lymphoma subtypes
cHL	Ref		Ref
sALCL	3.56(1.10–11.57)	0.035	3.27(0.97–11.02)	0.057
Othersa	10.09(3.46–29.42)	0.000	6.14(2.03–18.59)	0.001
Bone marrow involvement
Yes	3.35(1.60–7.02)	0.001	5.00(2.11–11.85)	0.000
No	Ref		Ref
CNS involvement
Yes	3.43(1.04–11.35)	0.043	5.40(1.41–20.64)	0.014
No	Ref		Ref
Line of BV-based therapy
First-line	0.61(0.29–1.28)	0.193	0.65(0.30–1.42)	0.283
Second- or later-line	Ref		Ref

Notes: ^aOthers include: nodal T-follicular helper cell lymphoma, peripheral T-cell lymphoma-not otherwise specified, diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, and primary cutaneous T-cell lymphoma.

Abbreviations: OS, overall survival; HR, hazard ratio; CI, confidence interval; cHL, classical Hodgkin lymphoma; sALCL, systemic anaplastic large cell lymphoma; ORR, overall response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; Ref, reference; CNS, central nervous system.

Discussion

In 2022, we first reported the real-world data from China to demonstrate the application of BV in clinical settings, based on a large patient cohort and the collaborative efforts of multiple institutions.2 This study laid a solid foundation for the broader adoption of BV in benefiting more lymphoma patients in China. However, due to the limited cohort size and short follow-up period, further analyses could not be conducted. Since then, the publication of additional domestic real-world clinical studies has further confirmed the efficacy and safety of BV in treating CD30-positive lymphoma patients in China, leading to its wider usage in recent years. In addition to cHL and sALCL, which are universally CD30-positive, BV has also been applied to other T-cell lymphomas and some B-cell lymphomas that express CD30. Moreover, the timing of BV administration has shifted to earlier stages of treatment. Building upon these developments, our present multicenter study provides an updated and more comprehensive real-world analysis from three major centers in Henan Province, featuring a larger cohort, longer follow-up, and detailed subgroup evaluation. This work fills the critical evidence gap between controlled clinical trials and real-world practice, reinforcing the therapeutic potential of BV across diverse lymphoma subtypes and offering new insights to optimize its clinical use in Chinese populations.

Our updated findings are consistent with our previous report published two years ago, further confirming the favorable effectiveness of BV in Chinese patients with CD30-positive lymphomas, particularly in cHL and sALCL, both of which are characterized by uniformly high CD30 expression. When comparing our findings with those from other Chinese real-world studies, the relatively less favorable outcomes observed in our cohort may be attributed to the larger proportion of R/R patients in each group.3–5 For other lymphoma types exhibiting varying degrees of CD30 expression, including PTCLs and DLBCL, approximately half of the patients in our study benefited from BV-based treatment. This may be linked to the distinct molecular profiles and heterogeneity of these subtypes.6,7 These subgroup analyses are exploratory and descriptive in nature, intended to illustrate the real-world treatment patterns and clinical applicability of BV rather than to make direct therapeutic comparisons. Due to the limited number of cases within each rare subtype, meaningful subtype-specific or stratified statistical analyses could not be performed. This limitation reflects the rarity and clinical diversity of some CD30-positive lymphomas encountered in real-world practice, and further large-scale studies are warranted to comprehensively evaluate BV’s effectiveness across individual lymphoma subtypes.

The safety profiles observed in our study were consistent with our previous findings, indicating that BV-based treatment was generally well tolerated. The incidence of PN did not show an increase compared to our historical reports, which may be attributed to our effective strategies in protecting nerve function during BV-containing regimens. These strategies include pharmacological prophylaxis such as applying neurotrophic agents (eg Methylcobalamin), and personal care strategies to keep their extremities warm and maintain appropriate limb care. BV has been demonstrated to be feasible for treating patients aged ≥60 years.8–10 In our study, although older patients experienced a higher frequency and greater severity of AEs, no AE-related mortality was reported. Given that leukopenia and infection were the most commonly observed grade ≥3 AEs, prophylactic use of granulocyte-colony stimulating factor (G-CSF) was deemed essential for older patients receiving BV-based regimens.

BV-based treatment regimens have been strongly recommended as first-line therapy for cHL and PTCL based on the impressive results from the ECHELON studies.11,12 In our real-world cohort, patients receiving BV in the first-line setting achieved a significantly higher CR rate compared with those treated in the second or later lines. However, given the retrospective nature of this study, treatment allocation was not randomized and may have been influenced by baseline prognostic characteristics, including disease burden, prior therapies, performance status, and overall clinical condition. Therefore, the improved outcomes observed in patients receiving frontline BV-based therapy may partly reflect underlying risk heterogeneity rather than a pure treatment effect. Previous studies have highlighted the importance and feasibility of developing validated prognostic models based on different treatment strategies to facilitate risk stratification and survival interpretation in Hodgkin lymphoma, emphasizing the challenges of distinguishing treatment-related benefit from baseline prognostic differences in real-world analyses.13 Although ORR, PFS, and OS were numerically improved in the frontline group, these differences did not reach statistical significance. To minimize the impact of confounding factors inherent in real-world studies, we further performed multivariate Cox regression analyses. In addition to variables showing associations in univariate analysis, clinically relevant prognostic factor such as Ann Arbor stage was incorporated into the multivariate model to ensure adequate adjustment, given their established prognostic significance in lymphoma and potential interaction with treatment line. Notably, BV treatment line was not identified as an independent predictor of either PFS or OS after adjustment. These findings suggest that while early use of BV may enhance depth of response, its effect on long-term survival remains uncertain in real-world practice. Residual confounding factors that were not fully captured in this retrospective analysis may also have influenced survival outcomes.

In cHL, the combination of BV with AVD was predominantly used as a first-line regimen. However, with several studies displaying the effectiveness of checkpoint inhibitors (CPIs) in first-line treatment,14–17 there is a growing potential for chemo-reduced or even chemo-free regimens for previously untreated cHL patients in the future. In the case of PTCLs, traditional CHOP-like regimens in the first-line setting have exhibited limited efficacy, with nearly 70% of patients progressing to R/R disease, resulting in poor prognostic outcomes.18 Consistent with other studies, we highlighted the clinical importance of BV-based combination therapy as a first-line approach for treating PTCL patients with variable CD30 expression.19,20 Regarding CTCL, BV is typically employed in patients who have previously undergone at least one systemic therapy, according to clinical trials.21,22 However, data on the application of BV-based first-line systemic therapy for CTCL are still scarce.23 In this report, we present four CTCL patients who were treated with BV-based regimens as first-line therapy, demonstrating acceptable effectiveness in this particular cohort.

Autologous or allogeneic hematopoietic stem cell transplantation (Auto-HSCT or Allo-HSCT) following salvage chemotherapy are well-established strategies for improving survival outcomes in R/R lymphoma patients, particularly in cHL. However, salvage chemotherapy regimens typically result in limited response rates (ORR of approximately 45–90%) and are often associated with high toxicity, which may lead to myelosuppression.24 In light of these challenges, BV monotherapy or its combination with chemotherapy prior to SCT has been recognized as a highly effective bridging therapy with mild toxicity for R/R patients who are unsuitable candidates for SCT following salvage chemotherapy.25,26 In our study, among 31 R/R patients who were ineligible for SCT due to insufficient response, the ORR reached 100% after BV-based bridge therapy, with 18 patients achieving CR and 13 patients achieving PR, successfully attaining deep remission prior to SCT. Furthermore, for approximately 50% of patients who would experience relapse after SCT, the median OS remained about 2 years, with limited treatment options available. Several clinical studies have underscored the role of BV as a consolidative treatment alternative for high-risk patients following SCT.27–30 In our study, BV monotherapy was predominantly used as post-SCT consolidation, achieving a 1-year OS rate of 100.0%, though more comprehensive clinical data are required. For patients who experienced failure after autologous HSCT, treatment regimens including BV, checkpoint inhibitors, chemotherapy, and allo-HSCT have been shown to improve survival outcomes.31,32

This study has several inherent limitations associated with its retrospective, real-world design. First, the retrospective nature inevitably introduces potential selection bias and confounding, as patients were not randomly assigned according to their BV-based treatment strategies. Treatment selection in clinical practice was influenced by multiple factors, including disease subtype, disease stage, treatment line, prior therapies, performance status, and even socioeconomic considerations, which could not be fully standardized or adjusted. Although efforts were made to collect comprehensive clinical data, unmeasured or overlapping variables may still have affected treatment outcomes. Second, the heterogeneity of lymphoma subtypes poses an additional challenge. The inclusion of multiple CD30-positive entities, such as cHL, sALCL, PTCL, DLBCL, and ENKTCL, reflects real-world clinical diversity but also limits the feasibility of subtype-specific analyses. In particular, the relatively small number of patients within certain rare subgroups precluded robust statistical comparisons and the application of more advanced adjustment approaches, such as propensity score matching or risk-stratified analyses, to further reduce confounding. Consequently, these limitations reduced the interpretability of our comparative outcomes across different treatment settings or patient subgroups. Third, the follow-up period, although longer than previous domestic reports, remains insufficient for assessing long-term survival outcomes or late-onset toxicities. Despite these limitations, our study represents one of the most comprehensive multicenter real-world analyses of BV in Chinese lymphoma patients to date. It not only reflects the evolving clinical adoption of BV across diverse disease contexts but also provides crucial insights into its effectiveness and safety under routine practice conditions, especially in first-line treatment and transplantation-related settings. Larger-scale, prospective multicenter studies with standardized protocols and control arms are warranted to validate our observations.

Conclusion

In summary, our updated analysis suggests that BV-based therapy demonstrated favorable effectiveness and manageable safety in Chinese patients with CD30-positive lymphomas in real-world clinical practice, including first-line and transplantation-related treatment settings. Nevertheless, in light of the retrospective design and the heterogeneity of lymphoma subtypes, future prospective multicenter clinical studies with better control of potential confounding factors are warranted to better define the optimal patient populations, treatment combinations, and sequencing strategies.

Funding Statement

The study was supported by National Natural Science Foundation of China (No.82170183), the Clinical Medical Scientist Training Program under the “Three 100s” Initiative of Henan Province(Grant No. HNCMS202428).

Data Sharing Statement

The original contributions presented in this study are included in the article, further inquiries can be directed to the corresponding author (Email: fcczhangxd@zzu.edu.cn).

Ethics Statement

The study was approved by the Clinical and Research Ethics Committee of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China (2022-KY-0869-001). Informed consent was obtained from all participants before receiving anti-tumor therapy.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

This paper is based on the abstract titled “Updated real-world outcomes with brentuximab vedotin in lymphoma patients: A multicenter, retrospective study from China” by professor Xudong Zhang. It has been published on the institutional website: https://doi.org/10.1182/blood-2025-7206.