Recent advances in single-cell multiomics have identified 3 distinct tumor microenvironment archetypes in diffuse large B-cell lymphoma (DLBCL), referred to as LymphoMAP archetypes: FMAC (enriched for tumor-associated fibroblasts and macrophages), LN (characterized by naïve and memory T cells), and TEX (marked by exhausted CD8-positive T cells). Prior work suggested that the FMAC subtype is associated with poorer outcomes when treated with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; Li et al, Cancer Cell, 2025), raising interest in whether novel regimens may overcome this disadvantage. The POLARIX trial previously demonstrated a sustained progression-free survival (PFS) and disease-free survival benefit with polatuzumab vedotin, a CD79b-targeting antibody–drug conjugate, plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) compared with R-CHOP, establishing it as a frontline option for patients with intermediate- to high-risk disease. In this exploratory analysis, investigators evaluated whether these benefits extend across LymphoMAP-defined subtypes.

Gene expression profiling data were available for 669 patients enrolled in POLARIX, including 331 treated with Pola-R-CHP and 338 with R-CHOP. The distribution of LymphoMAP archetypes was relatively balanced: 33.5% FMAC, 34.2% LN, and 29.3% TEX. Baseline characteristics were generally comparable across groups, although LN cases were less likely to have high International Prognostic Index scores, and TEX cases were more frequently associated with activated B-cell (ABC)-DLBCL.

With a median follow-up of just over 5 years, Pola-R-CHP demonstrated a consistent trend toward improved PFS across all 3 microenvironment subtypes. The greatest benefit was observed in the FMAC group, where the adjusted hazard ratio (HR) for PFS was 0.66 (95% CI, 0.43-1.01). Improvements were also seen in the LN (HR, 0.79; 95% CI, 0.51-1.23) and TEX (HR, 0.81; 95% CI, 0.50-1.32) subtypes, although CIs crossed unity, reflecting the exploratory nature of the analysis. The magnitude of benefit was most pronounced in the FMAC subgroup, historically associated with inferior outcomes. In the FMAC subtype, Pola-R-CHP was associated with a notable improvement in 5-year overall survival corresponding to an HR of 0.64, while HRs in LN and TEX (0.93 and 0.92) remained closer to unity and were not statistically significant. Furthermore, Pola-R-CHP improved PFS in patients with ABC-DLBCL.

Overall, this analysis highlights the potential relevance of tumor microenvironment classification in understanding treatment outcomes in DLBCL. Although Pola-R-CHP appears to confer benefit across all LymphoMAP subtypes, the greatest advantage may lie in the FMAC group, which has historically been associated with a poorer prognosis. Prospective validation will be needed to confirm the predictive value of LymphoMAP subtypes and to refine patient selection for novel frontline therapies.

Source: Harkins RA, et al. Outcomes by LymphoMAP archetypes in untreated diffuse large B-cell lymphoma from the POLARIX trial. Presented at: ASCO Annual Meeting. May 29-June 2, 2026; Chicago, IL. Abstract 7017.