BACKGROUND: Real-world patients receiving a bispecific therapy (epcoritamab or glofitamab) for third-line plus (3L+) treatment for relapsed/refractory Diffuse Large B-Cell Lymphoma (DLBCL) are often medically complex due to prior treatments, co-morbidities and other patient characteristics. Pre-specification of prognostic factors is necessary in order to adjust or stratify patients based on known confounding variables to contextualize study findings. A 2025 systematic literature review identified 36 prognostic factors significantly associated with clinical outcomes in R/R DLBCL, and lymphoma clinical experts prioritized and ranked 10 as key for inclusion when evaluating third-line interventions.

OBJECTIVE: The objective of this study was to assess how frequently real-world evidence (RWE) studies on bispecifics in R/R DLBCL report, adjust for, or stratify results by the top 10 expert-ranked prognostic factors.

METHODS: A targeted literature review was conducted to identify RWE studies published between January 1, 2023, and June 30, 2025. PubMed and Google Scholar were searched to identify RWE publications (abstracts, posters, oral presentations, manuscripts, editorials) using search terms related to DLBCL, bispecific antibodies (epcoritamab, glofitamab), and real-world study designs (observational, retrospective, expanded access, registry). Relevant congress websites were searched for additional publications. Eligible studies met the following criteria: 1) evaluated epcoritamab, glofitamab, or both; 2) included ≥50% of patients with R/R DLBCL receiving 3L+ bispecific therapy; and 3) reported effectiveness outcomes, such as response or survival.

Data were extracted on study characteristics, bispecific antibody studied, and reporting of the 10 expert-ranked prognostic factors: Early Chemo-Immunotherapy Failure/Primary Refractory Disease, Eastern Cooperative Oncology Group (ECOG) Performance Status, Refractory to Last Line of Therapy (LoT), Number of Prior LoTs, Double- or Triple-hit Lymphoma, Age at Start of LoT, International Prognostic Index Classification, Ann Arbor Disease Stage, Serum LDH, and Deauville Score. Each factor was assessed for whether it was (a) descriptively reported and/or (b) analyzed through adjustment or stratification.

RESULTS: Twenty-two studies were identified, including three manuscripts, one letter to the editor, and 18 abstracts (five with available posters or oral presentations). Four studies (18%) focused on epcoritamab, 10 (45%) on glofitamab, and 8 (35%) on both therapies.

While all studies descriptively reported at least one of the top 10 expert-ranked factors (median 6 factors; range 2-8), less than half (45%) included at least one factor in effectiveness analyses (median 0 factors, range 0-6). None reported or analyzed all 10 factors.

Age at start of LoT (factor #5) was the most frequently reported factor (all studies); Deauville Score (factor #10) was the least (no studies). Serum LDH (factor #8) was the most commonly analyzed factor (32%), and Deauville Score was the least (no studies).

Among the top three expert-ranked factors (Early Chemo-Immunotherapy Failure/Primary Refractory Disease, ECOG Status, Refractory to Last LoT), few studies reported (9%) or analyzed (5%) all three. Early Chemo-Immunotherapy Failure—the top-ranked factor—was reported in 23% of studies and analyzed in 9%. The two factors with a priority #2 ranking, ECOG Status and Refractory to Last LoT, were each descriptively reported in about half of studies but analyzed as a covariate in only four of twenty-two studies (18%).

Among the three manuscripts presenting comprehensive results, Early Chemo-Immunotherapy Failure/Primary Refractory Disease was reported in two studies (2/3, 67%) and analyzed in one (1/3, 33%), ECOG Status was reported in all three studies and analyzed in one (1/3, 33%), and Refractory to Last LoT was reported in one (1/3, 33%) and analyzed in none.

CONCLUSION: Although often reported descriptively, expert-prioritized prognostic factors are rarely incorporated into RWE analyses on bispecific effectiveness in R/R DLBCL. The highest-priority factors identified by experts are not consistently reported or analyzed, potentially due to missing data, small sample sizes, or lack of availability in administrative datasets. To better contextualize treatment outcomes in this complex patient population, future real-world studies should describe and control for these key prognostic variables.

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2025
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