What Real-World Data Reveal About R/R DLBCL Care

Key Takeaways

• Lack of standardized care in later lines: The absence of a dominant regimen in third-line (3L) and fourth-line (4L) settings complicates formulary design and may necessitate flexible, individualized approaches to coverage.
• Underutilization of high-cost novel therapies: Low uptake of chimeric antigen receptor (CAR) T-cell and targeted therapies suggests access, cost, or infrastructure barriers that may need policy reassessment.
• Continued reliance on rituximab-based regimens: High utilization of rituximab combinations indicates a need to reassess value frameworks for legacy therapies versus newer alternatives.
• Rapid treatment failure in later lines: Short treatment durations in later lines indicate high unmet need and may support coverage of more effective novel options.
• Access and sequencing challenges: The growing number of options combined with limited guidance on treatment sequencing underscores the need for real-world evidence to inform reimbursement and pathway decisions.

A large, contemporary analysis of US real-world data underscores significant variability in treatment patterns for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with no clear standard of care emerging in later lines of therapy. The findings raise important considerations for payers and managed care stakeholders as the therapeutic landscape continues to expand.

Study Findings

The retrospective study analyzed claims from two major databases—MarketScan and Symphony Health—capturing more than 52 000 adult patients who initiated first-line DLBCL treatment between 2017 and 2024. Despite the introduction of multiple novel therapies in recent years, the analysis found that treatment approaches remain highly heterogeneous, particularly in 3L and 4L settings.

Across both datasets, rituximab-based regimens dominated treatment patterns beyond first-line (1L) therapy. More than half of patients in second-line (2L) and later lines received rituximab-containing therapies, often in various combinations. However, utilization of newer agents—including CAR T-cell therapies, antibody-drug conjugates, and bispecific antibodies (BsAbs)—remained notably low.

“The heterogeneity of treatments observed in our analyses suggests that no single therapy demonstrates sufficient efficacy in this population to be considered the standard of care in later-line settings,” the study authors noted.

Despite regulatory approvals and clinical promise, newer therapies showed minimal real-world adoption. CAR T-cell therapy, for example, was used in fewer than 5% of patients in later lines in MarketScan and approximately 0.1%–1.8% in Symphony data. Similarly, other targeted agents such as polatuzumab vedotin, tafasitamab, and loncastuximab tesirine were used in only a small fraction of patients. These findings suggest potential barriers to access, including cost, infrastructure requirements, patient eligibility, and logistical complexity—factors highly relevant to coverage policy decisions.

The study also revealed steep attrition across lines of therapy. Only about 20% of patients progressed from 1L to 2L treatment, and approximately 7% reached 3L therapy. By 4L, just 2%–3% of the original cohort remained. Treatment duration shortened substantially with each subsequent line, dropping to less than 1 month in 3L and 4L settings, indicating rapid treatment failure or discontinuation. At the same time, time to next treatment exceeded treatment duration in later lines, suggesting delays between therapy discontinuation and initiation of subsequent treatment.

Implications for Coverage, Access, and Care Delivery

As treatment options proliferate, the absence of clear sequencing guidance complicates clinical decision-making and reimbursement strategies. The continued reliance on older, familiar regimens such as rituximab-based therapies may reflect both physician comfort and uncertainty around optimal use of newer agents. For payers, these findings highlight the tension between innovation and real-world feasibility, as novel therapies with demonstrated clinical benefit remain underutilized in routine practice.

The evolving R/R DLBCL treatment landscape presents both opportunities and challenges for healthcare stakeholders. While therapeutic innovation continues, real-world data reveal persistent gaps in effectiveness, access, and standardization—areas that will be critical for future policy and reimbursement strategies.

Reference

Phillips T, Zhou Z, Gutierrez C, et al. Real-world treatment patterns and characteristics of patients with diffuse large B-cell lymphoma (DLBCL): a retrospective analysis of US commercial and Medicare claims (2017–2024). Leukemia & Lymphoma. 2026;67(3):627-637. doi:10.1080/10428194.2025.2604300