Frontline Landscape Overview and Biomarker Testing in DLBCL

Dr. Jason Westin introduces the program on optimizing treatment strategies in DLBCL, joined by Drs. Tara Graff, Patrick Connor Johnson, and Matthew Lunning. The discussion covers the current first-line landscape, new Phase 3 data, frontline patient selection, and the evolving relapsed/refractory setting where bispecific antibodies are reshaping standards.

Dr. Graff describes practice evolution over the past 3 years, noting that polatuzumab vedotin-R-CHP (Pola-R-CHP) has become her standard approach, a shift she contrasts with earlier concerns about moving away from dose-adjusted R-EPOCH in higher-risk patients. She emphasizes that community adoption, though sometimes slower, has accelerated given prior comfort with polatuzumab from relapsed/refractory use. She advocates for routine cell-of-origin testing by immunohistochemistry as a standard component of DLBCL pathology workup, noting that institutional education of pathology teams is necessary to ensure consistent testing rather than ad hoc ordering.

Dr. Johnson identifies key drivers of R-CHOP failure: high International Prognostic Index scores (IPI 4-5), MYC and BCL-2 rearrangements defining high-grade B-cell lymphoma (so-called double-hit disease), and double expressers (patients who overexpress both MYC and BCL-2 protein without underlying FISH translocations). He highlights emerging molecular classification systems including LymphGen subtypes and tumor microenvironment archetypes, noting that the MCD subtype with MYD88 and CD79B alterations may be particularly relevant for BTK inhibitor-based approaches.

Dr. Lunning describes his approach to Pola-R-CHP, broadly offering it to IPI 2 to 5 patients while acknowledging trial exclusions such as transformed follicular lymphoma require individual judgment. He praises POLARIX's randomized double-blind design, which demonstrated progression-free survival advantage with a comparable toxicity profile to vincristine-containing regimens.