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Peer-reviewedCC BY 4.0Frontiers in Immunology

Sintilimab plus R-CHOP versus DA-EPOCH-R as first-line therapy for primary mediastinal large B-cell lymphoma: a real-world comparative cohort study

  1. 1Department of Lymphoma, the Affiliated Hospital of Qingdao University
  2. 2Department of Oncology, Gaomi People’s Hospital
  3. 3Department of Hematology, Linyi Central Hospital

Abstract

Background: Primary mediastinal large B-cell lymphoma (PMBCL) is a highly curable lymphoma in which first-line therapy must balance durable disease control with acute and late treatment toxicity.

Methods: We retrospectively analyzed 98 patients with newly diagnosed PMBCL who received sintilimab plus R-CHOP (group 1, n = 42) or DA-EPOCH-R (group 2, n = 56). The primary endpoint was progression-free survival (PFS), and secondary endpoints included complete metabolic response (CMR) and safety. Propensity-score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to adjust for baseline imbalances. Molecular profiling was performed in 75 diagnostic samples to characterize immune-escape features, including 9p24.1 alterations and PD-L1/PD-L2 expression.

Results: Sintilimab plus R-CHOP produced numerically comparable response and PFS outcomes to DA-EPOCH-R, although equivalence or non-inferiority cannot be inferred from this retrospective, event-limited cohort. CMR rates were 85.7% versus 83.9% before matching (Fisher P = 1.000) and 83.3% versus 80.6% after PSM (P = 1.000; 36 pairs). Estimated 24-, 36-, and 60-month PFS rates were 81.0% versus 83.9% before matching (HR 1.19, 95% CI 0.46–3.09; log-rank P = 0.716), 83.3% versus 80.6% after matching (HR 0.84, 95% CI 0.28–2.51; P = 0.759), and 83.9% versus 84.6% after IPTW (HR 1.04, 95% CI 0.39–2.76; robust P = 0.942), respectively. These estimates were based on 17 PFS events in the full cohort and 13 events after matching. Grade 3–4 neutropenia was less frequent with sintilimab plus R-CHOP before matching (38.1% versus 66.1%; P = 0.008) and remained lower after matching (30.6% versus 61.1%; P = 0.017). In 75 profiled diagnostic samples, group-level molecular data confirmed the expected immune-escape architecture of PMBCL and showed broadly similar distributions of 9p24.1 alterations and PD-L1/PD-L2 expression between treatment groups.

Conclusion: In this real-world cohort, sintilimab plus R-CHOP produced overlapping response and PFS estimates relative to DA-EPOCH-R, together with less grade 3–4 neutropenia. The study cannot establish equivalence, non-inferiority, treatment replacement, or radiotherapy omission. These findings support the biological rationale for integrating PD-1 blockade into frontline chemoimmunotherapy and highlight the need for prospective studies to define its role within PET-adapted and immune-driven treatment strategies for PMBCL.

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BibTeX
@article{liu2026sintilimab,
  title = {{Sintilimab plus R-CHOP versus DA-EPOCH-R as first-line therapy for primary mediastinal large B-cell lymphoma: a real-world comparative cohort study}},
  author = {Zhihe Liu and Jianxin Ren and Kaiqin Jiang and Hao Guan and Xia Zhao},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1924360},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1924360/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Sintilimab plus R-CHOP versus DA-EPOCH-R as first-line therapy for primary mediastinal large B-cell lymphoma: a real-world comparative cohort study
AU  - Zhihe Liu
AU  - Jianxin Ren
AU  - Kaiqin Jiang
AU  - Hao Guan
AU  - Xia Zhao
PY  - 2026
DA  - 2026/10/13
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1924360
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1924360/full
AB  - Background: Primary mediastinal large B-cell lymphoma (PMBCL) is a highly curable lymphoma in which first-line therapy must balance durable disease control with acute and late treatment toxicity.  Methods: We retrospectively analyzed 98 patients with newly diagnosed PMBCL who received sintilimab plus R-CHOP (group 1, n = 42) or DA-EPOCH-R (group 2, n = 56). The primary endpoint was progression-free survival (PFS), and secondary endpoints included complete metabolic response (CMR) and safety. Propensity-score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to adjust for baseline imbalances. Molecular profiling was performed in 75 diagnostic samples to characterize immune-escape features, including 9p24.1 alterations and PD-L1/PD-L2 expression.  Results: Sintilimab plus R-CHOP produced numerically comparable response and PFS outcomes to DA-EPOCH-R, although equivalence or non-inferiority cannot be inferred from this retrospective, event-limited cohort. CMR rates were 85.7% versus 83.9% before matching (Fisher P = 1.000) and 83.3% versus 80.6% after PSM (P = 1.000; 36 pairs). Estimated 24-, 36-, and 60-month PFS rates were 81.0% versus 83.9% before matching (HR 1.19, 95% CI 0.46–3.09; log-rank P = 0.716), 83.3% versus 80.6% after matching (HR 0.84, 95% CI 0.28–2.51; P = 0.759), and 83.9% versus 84.6% after IPTW (HR 1.04, 95% CI 0.39–2.76; robust P = 0.942), respectively. These estimates were based on 17 PFS events in the full cohort and 13 events after matching. Grade 3–4 neutropenia was less frequent with sintilimab plus R-CHOP before matching (38.1% versus 66.1%; P = 0.008) and remained lower after matching (30.6% versus 61.1%; P = 0.017). In 75 profiled diagnostic samples, group-level molecular data confirmed the expected immune-escape architecture of PMBCL and showed broadly similar distributions of 9p24.1 alterations and PD-L1/PD-L2 expression between treatment groups.  Conclusion: In this real-world cohort, sintilimab plus R-CHOP produced overlapping response and PFS estimates relative to DA-EPOCH-R, together with less grade 3–4 neutropenia. The study cannot establish equivalence, non-inferiority, treatment replacement, or radiotherapy omission. These findings support the biological rationale for integrating PD-1 blockade into frontline chemoimmunotherapy and highlight the need for prospective studies to define its role within PET-adapted and immune-driven treatment strategies for PMBCL.
SN  - 1664-3224
ER  -