Dr Shadman on the Need for a Clinical Consensus in the Evolving Treatment Landscape of DLBCL

Mazyar Shadman, MD, MPH, Innovators Network Endowed Chair, associate professor, Clinical Research Division, Fred Hutchinson Cancer Center; associate professor, Medical Oncology Division, University of Washington School of Medicine, discusses the complexities of treatment selection in diffuse large B-cell lymphoma (DLBCL) as novel agents continue to reshape frontline therapy. With emerging data and multiple active regimens available, treatment decisions increasingly rely on expert consensus rather than direct head-to-head comparisons. These considerations were discussed at the Bridging The Gaps: Leukemia, Lymphoma, and Multiple Myeloma meeting in Miami, Florida.

DLBCL treatment has historically centered around R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as the standard first-line regimen. However, the addition of polatuzumab vedotin (Polivy) to a similar backbone (Pola-R-CHP) has demonstrated improved progression-free survival, positioning it as a preferred first-line therapy. Despite this advancement, Shadman highlights the ongoing challenge of determining which patient populations derive the greatest benefit from Pola-R-CHP vs other emerging chemoimmunotherapy combinations.

Another key consideration is patient selection and stratification, he explains. Identifying subgroups based on clinical and molecular factors, such as high-risk cytogenetics or advanced disease burden, is critical in tailoring frontline therapy. However, without head-to-head randomized trials comparing different regimens, treatment decisions must rely on expert interpretation of existing data, he adds. Further complicating treatment selection is the heterogeneity of DLBCL subtypes, which may require different therapeutic approaches.

Shadman underscores the importance of expert consensus in bridging the gap between clinical trial data and real-world practice, particularly in community oncology settings where access to emerging therapies may vary. Standardized treatment guidelines would help establish criteria for selecting Pola-R-CHP vs other frontline regimens, determine the optimal sequencing of novel agents, and refine treatment strategies based on patient-specific risk factors.

Future prospective studies remain necessary to clarify several key aspects of DLBCL management, including the role of targeted therapies in the frontline setting, optimal sequencing strategies, and the integration of biomarkers for risk stratification. Establishing a consensus through expert collaboration is essential in optimizing outcomes and ensuring that new therapeutic advances are effectively incorporated into clinical practice.