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Clinical Outcomes of Treatment-Naive Transformed vs. De Novo Diffuse Large B-Cell Lymphoma: A Propensity Score-Matched Analysis of 1735 Cases
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, China
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Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2026, 18(10), 1641; https://doi.org/10.3390/cancers18101641
Submission received: 17 April 2026
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Revised: 15 May 2026
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Accepted: 18 May 2026
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Published: 19 May 2026
(This article belongs to the Section Clinical Research of Cancer)
Simple Summary
Diffuse large B-cell lymphoma (DLBCL) can arise as a new diagnosis (de novo) or through the transformation of a pre-existing indolent lymphoma (trDLBCL). Whether trDLBCL carries a worse prognosis in treatment-naive patients remains a subject of debate. In this large-scale study of 1735 patients, we used propensity score matching to compare the clinical outcomes of these two groups. Our results show that while patients with trDLBCL have a higher risk of early disease progression (POD24) and significantly shorter progression-free survival (PFS), their overall survival (OS) is comparable to that of those with de novo DLBCL, likely due to effective subsequent salvage therapies. Importantly, we identified that “pure transformation” (patients without a concurrent indolent component at diagnosis) represents an ultra-high-risk subgroup with markedly worse outcomes. These findings emphasize that trDLBCL is a distinct clinical entity requiring more intensive or risk-adapted frontline treatment strategies to prevent early relapse and overcome intrinsic therapy resistance.
Abstract
Background: The prognostic significance of histological transformation (HT) in treatment-naive diffuse large B-cell lymphoma (DLBCL) remains controversial. This study aimed to evaluate the clinical outcomes and failure patterns of treatment-naive transformed DLBCL (trDLBCL) compared with de novo DLBCL using a large-scale cohort. Methods: We retrospectively analyzed 1735 consecutively enrolled treatment-naive DLBCL patients (118 trDLBCL and 1617 de novo). Propensity score matching (PSM) was performed to balance baseline characteristics. Survival outcomes were assessed using Kaplan–Meier and Cox proportional hazards models. Subgroups were defined by pathology (t-FL vs. t-MZL) and pattern: concurrent (synchronous indolent lymphoma and DLBCL components at diagnosis)vs. pure transformation (DLBCL occurring as the sole histology in patients with a prior history of untreated indolent lymphoma). Results: In the overall cohort, trDLBCL was associated with significantly inferior progression-free survival (PFS) compared with de novo disease and remained an independent adverse prognostic factor in multivariable analysis (HR 1.754, p < 0.001). These findings were confirmed in a 1:1 propensity score-matched cohort (108 pairs), where trDLBCL continued to show worse PFS (p < 0.01), while overall survival (OS) was comparable (p = 0.99). Within trDLBCL patients, the underlying indolent subtype (t-FL vs. t-MZL) did not significantly affect survival (PFS p = 0.17, OS p = 0.35), whereas “pure transformation” was associated with markedly inferior PFS (p = 0.005) and OS (HR 2.56, p = 0.02) compared with concurrent transformation. Failure pattern analysis revealed a higher risk of early progression in trDLBCL (POD24: 30.56% vs. 18.52%; OR 1.94, 95% CI: 1.05–3.56), whereas central nervous system (CNS) involvement was low and comparable between groups (2.78% vs. 0.93%, p = 0.62). Conclusions: Treatment-naive trDLBCL is associated with inferior PFS driven by early progression, whereas OS is comparable due to effective salvage therapies. Pure transformation appeared to define a higher-risk subgroup with inferior disease control, supporting the need for future prospective studies to evaluate risk-adapted frontline, consolidation, or maintenance strategies.
