Glofitamab <i>vs.</i> real-world regimens in Chinese patients with third- or later-line relapsed/refractory diffuse large B-cell lymphoma: an external control study

Glofitamab vs. real-world regimens in Chinese patients with third- or later-line relapsed/refractory diffuse large B-cell lymphoma: an external control study

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Keshu Zhou¹, Huijing Wu², Xia Zhao³, Xiaohong Tan⁴, Xiaojing Yan⁵, Haisheng Liu⁶, Liping Su⁷, Yukun Lan⁸, Jaihui Xu⁸, Xiaohui Zhou⁸, Yuerong Shuang⁹, Huilai Zhang¹⁰

Cancer Biology & Medicine | 2025, 22(10) : 1218 - 1222

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Cancer Biology & Medicine | 2025, 22(10): 1218-1222

• Letter •

Glofitamab vs. real-world regimens in Chinese patients with third- or later-line relapsed/refractory diffuse large B-cell lymphoma: an external control study

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Keshu Zhou¹, Huijing Wu², Xia Zhao³, Xiaohong Tan⁴, Xiaojing Yan⁵, Haisheng Liu⁶, Liping Su⁷, Yukun Lan⁸, Jaihui Xu⁸, Xiaohui Zhou⁸, Yuerong Shuang⁹, Huilai Zhang¹⁰

Affiliations

¹Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450003, China

²Department of Oncology, Hubei Cancer Hospital, Wuhan 430079, China

³Department of Lymphoma, The Affiliated Hospital of Qingdao University, Qingdao 266003, China

⁴Department of Haematology/Oncology and Paediatric Oncology, Guangxi Medical University Affiliated Cancer Hospital, Nanning 530021, China

⁵Department of Hematology, The First Hospital of China Medical University, Shenyang 110001, China

⁶Department of Hematology, The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital, Shijiazhuang 050011, China

⁷Department of Hematology, Shanxi Cancer Hospital Institute, Taiyuan 030013, China

⁸Shanghai Roche Pharmaceuticals Ltd., Shanghai 201203, China

⁹Department of Lymphatic and Hematological Oncology, Jiangxi Cancer Hospital, Nanchang 330029, China

¹⁰Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

About Author:

Author contributions

Conceptualization: Keshu Zhou, Huilai Zhang, Yuerong Shuang, Xiaohui Zhou, and Yukun Lan.

Data curation: Keshu Zhou, Huijing Wu, Xiaohui Zhou, Xiaohong Tan, Xiaojing Yan, Haisheng Liu, Liping Su, Yuerong Shuang, and Huilai Zhang.

Formal analysis: Yukun Lan, Xiaohui Zhou, and Jaihui Xu.

Investigation: All authors.

Methodology: Xiaohui Zhou and Yukun Lan.

Supervision: Keshu Zhou, Huilai Zhang, Yukun Lan, and Xiaohui Zhou.

Validation: All authors.

Writing—Original draft: All authors.

Writing—Review & editing: All authors.

Published: 2025-10-15 doi: 10.20892/j.issn.2095-3941.2025.0104

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Cite this Article

Keshu Zhou, Huijing Wu, Xia Zhao, Xiaohong Tan, Xiaojing Yan, Haisheng Liu, Liping Su, Yukun Lan, Jaihui Xu, Xiaohui Zhou, Yuerong Shuang, Huilai Zhang. Glofitamab vs. real-world regimens in Chinese patients with third- or later-line relapsed/refractory diffuse large B-cell lymphoma: an external control study[J]. Cancer Biology & Medicine, 2025 , 22 (10) : 1218 -1222 . DOI: 10.20892/j.issn.2095-3941.2025.0104

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Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin’s lymphoma (NHL) worldwide, accounts for 39% and 44% of nodal and extranodal NHL cases in China, respectively¹. Standard first-line treatment for DLBCL is chemo-immunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, which cures 50%–60% of patients². Therefore, approximately 40% of DLBCL patients are refractory to or relapse after treatment. Glofitamab is a T cell-engaging bispecific monoclonal antibody targeting CD20 expressed on B cells and CD3 on the surface of T cells, inducing tumor cell lysis and T cell activation, proliferation, and cytokine release³. Glofitamab has promising efficacy and safety in global and Chinese phase 1/2 studies involving patients with relapsed/refractory DLBCL^4,5 with overall response rates (ORRs) of 52% and 67% and complete response rates (CRRs) of 40% and 52%, respectively^4–6. Among these studies the most common adverse event (AE) was cytokine release syndrome (63%)^4,6. Indeed, the incidence of grade ≥ 3 cytokine release syndrome was 4%⁴. Based on these promising results, glofitamab was approved for the treatment of relapsed/refractory DLBCL in China in November 2023. However, clinical studies comparing glofitamab with regimens frequently used in real-world Chinese practice are lacking. Therefore, this study aimed to compare the efficacy and safety of glofitamab versus real-world regimens in Chinese patients with third- or later-line relapsed/refractory DLBCL.

This study compared data from a multicenter glofitamab cohort with an external control [real-world data (RWD) cohort]. The study schema for the glofitamab cohort and observation period is provided in Figure S1. The glofitamab cohort was constructed using data from a prospective, open-label, single-arm phase 1 study conducted in five sites in China⁶. The RWD cohort was derived from a non-interventional, retrospective, observational cohort involving secondary data use with information originating from routine clinical practice. The primary efficacy endpoint was CRR. The secondary endpoints were ORR and time-to-next treatment (TTNT). The exploratory endpoints included the incidence and severity of hematologic AEs with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0) and routine blood laboratory tests (neutrophil count, white blood cell count, platelet count, hemoglobin concentration, and bilirubin, creatinine, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase levels). Additional details regarding the study design, study population, endpoint definitions, and statistical analysis are provided in the Supplementary methods.

The patient disposition is shown in Figure S2. In total, 30 (100%) and 27 (90.0%) patients were included in the glofitamab safety set and full analysis set (FAS), respectively. The final FAS and safety set for the RWD cohort included 162 (73.6%) patients. Baseline covariates for inverse probability weighting-average treatment effect on the treated weights using the propensity score method are summarized in Table S1. The median (min, max) treatment duration was 24.9 (0, 39) weeks in the glofitamab cohort and 4.0 (0, 65) weeks in the RWD cohort. The median [95% confidence interval (CI)] follow-up time was 14.52 (13.50, 19.68) months in the glofitamab cohort and 17.74 (10.78, 28.48) months in the weighted RWD cohort.

CRR

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The unweighted CRR was 51.9% (95% CI: 31.95%, 71.33%) in the glofitamab cohort. The unweighted and weighted CRRs were 9.9% (95% CI: 5.75%, 15.54%) and 10.1% (95% CI: 0.00%, 21.38%) in the RWD cohort, respectively (Table 1). The CRR for the glofitamab cohort was significantly higher than the RWD cohort in the weighted [rate difference (95% CI): 41.8% (19.80%, 63.76%), odds ratio (95% CI): 9.617 (2.235, 41.383); P = 0.0024] and unweighted groups [rate difference: 42.0% (22.58%, 61.37%), odds ratio: 9.827 (3.938, 24.523); P < 0.0001].

ORR and TTNT

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The unweighted ORR was 66.7% (95% CI: 46.04%, 83.48%) in the glofitamab cohort. The unweighted and weighted ORRs were 30.2% (95% CI: 23.29%, 37.95%) and 31.1% (95% CI: 13.72%, 48.52%) in the RWD cohort, respectively (Table 1). The ORR for the glofitamab cohort was significantly higher than the RWD cohort in the weighted [rate difference (95% CI): 35.5% (10.67%, 60.42%), odds ratio (95% CI): 4.426 (1.416, 13.837); P = 0.0105] and unweighted groups [rate difference: 36.4% (17.28, 55.56), odds ratio 4.612 (1.937, 10.982); P = 0.0002].

The median (95% CI) TTNT was not reached (6.64 months, not estimated) in the glofitamab cohort. The median (95% CI) TTNT was 3.84 (3.02, 5.52) and 3.94 (2.83, 7.52) months in the unweighted and weighted RWD cohorts, respectively. The 12-month TTNT rate (95% CI) was 60.9% (41.92%, 79.88%) in the glofitamab cohort, 29.8% (21.59%, 37.96%) in the unweighted RWD cohort (Figure 1A), and 30.6% (19.96%, 41.23%) in the weighted RWD cohort (Figure 1B). Hazard ratios (95% CI) in the glofitamab cohort for TTNT versus the RWD cohort were 0.432 (0.231, 0.808; P = 0.0086) before weighting and 0.450 (0.208, 0.974; P = 0.0426) after weighting.

Safety

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The incidence rate (95% CI) of hematologic AEs was 56.7% (37.4%, 74.5%) in the glofitamab cohort, 60.5% (52.5%, 68.1%) in the unweighted RWD cohort, and 60.9% (43.5%, 78.3%) in the weighted RWD cohort. There were no significant differences in the incidence rate of hematologic AEs in the glofitamab cohort versus the unweighted RWD cohort [odds ratio (95% CI): 0.854 (0.388, 1.878); P = 0.6944] or the weighted RWD cohort [0.839 (0.300, 3.331); P = 2.343]. Table S2 lists the hematologic AEs reported during this study. Table S3 summarizes the key changes in routine blood tests from baseline-to-worst post-baseline measure by clinical significance in the RWD cohort.

Sensitivity analysis

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Sensitivity analysis showed that glofitamab was associated with significantly greater CRRs and ORRs, as well as longer TTNTs compared to the unweighted and weighted RWD cohorts, even after considering patients without prior chimeric antigen receptor T therapy and using an alternate definition of TTNT.

CRRs and ORRs improved with glofitamab compared to frequently used real-world regimens. The higher CRRs in the glofitamab cohort compared to the RWD cohort could indicate that patients with DLBCL have deeper tumor responses. The findings are supported by previous studies in which other bispecific antibodies were used^7,8. The 12-month TTNT rate was significantly higher in the glofitamab cohort than the RWD cohort, indicating a longer remission time for patients with DLBCL treated with glofitamab compared to patients receiving other therapies in a real-world setting. These findings are consistent with previous clinical trial data that demonstrated prolonged TTNTs with bispecific antibody therapies versus standard treatments or historical controls^8,9. In addition, the findings of the current study supported the existing literature regarding the safety of glofitamab¹⁰. The present study had some limitations, including the variability of data sources, retrospective RWD cohort data, lack of control over the study variables and potential unmeasured factors, and reliance on existing data sources that may result in incomplete or inconsistent data. Residual confounding may have existed even though the key prognostic factors were adjusted, which bias efficacy comparisons due to the limited sample size and an inability to adjust for all prognostic factors.

In conclusion, the glofitamab cohort had a favorable efficacy profile compared to RWD cohorts across various endpoints, with better tumor responses, longer response times, and generally better hematologic safety profiles than frequently used therapies in real-world settings among Chinese patients with relapsed/refractory DLBCL. These results supplement existing evidence from previous studies comparing bispecific antibodies with real-world regimens for relapsed/refractory DLBCL, filling gaps in comparative data, and therefore may provide guidance for clinicians making therapeutic choices in real-world clinical practice.

Funding

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This study was sponsored by Shanghai Roche Pharmaceuticals Ltd.

References

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Shirley M.Glofitamab: first approval.Drugs.2023; 83: 935–41.

Dickinson MJ,Carlo-Stella C,Morschhauser F,Bachy E,Corradini P,Iacoboni G, et al.Glofitamab for relapsed or refractory diffuse large B-cell lymphoma.N Engl J Med.2022; 387: 2220–31.

Hutchings M,Carlo-Stella C,Morschhauser F,Falchi L,Bachy E,Cartron G, et al.ABCL-340 Glofitamab monotherapy in relapsed or refractory large B-cell lymphoma: extended follow-up from a pivotal phase 2 study and subgroup analyses in patients with prior chimeric antigen receptor T-cell therapy and by baseline total metabolic tumor volume.Clin Lymphoma Myeloma.2024; 24: S473.

Song YQ,Zhang HL,Huang HQ,Zhang QY,Jing HM,Wang C, et al.Glofitamab monotherapy induces high complete response rates and manageable safety in Chinese patients with heavily pretreated relapsed or refractory diffuse large B-cell lymphoma.Haematologica.2024; 109: 1269–73.

Ip A,Rosenthal A,Mutebi A,Wang T,Jun M,Wang A, et al.P1169: Comparison of real-world clinical outcomes in patients with relapsed/refractory large B-cell lymphoma treated with epcoritamab vs chemoimmunotherapy.Hemasphere.2023; 7: e324937a.

McGough SF,Shamas N,Wang J,Jaber M,Swarup B,Blanchet Zumofen MH, et al.Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy.Leuk Lymphoma.2023; 64: 2269–78.

Sehn LH,Bartlett NL,Matasar MJ,Schuster SJ,Assouline SE,Giri P, et al.Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥ 2 prior therapies.Blood.2025; 145: 708–19.

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Saleh K,Khoury R,Khalife N,Chahine C,Ibrahim R,Tikriti Z, et al.The evolving role of bispecific antibodies in diffuse large B-cell lymphoma.J Pers Med.2024; 14: 666.

Appendix

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Year 2025 volume 22 Issue 10

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Article Info

doi: 10.20892/j.issn.2095-3941.2025.0104

Receive Date：2025-05-08
Online Date：2026-11-07
Published：2025-10-15

Article Data

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History

Received：2025-05-08
Accepted：2025-08-06

Funding

This study was sponsored by Shanghai Roche Pharmaceuticals Ltd.

Affiliations