Glofitamab (CD20xCD3) + polatuzumab vedotin (CD79b ADC) blunts high-risk biology signals in R/R LBCL biomarker analysis

Glofitamab is a CD20xCD3 T-cell–engaging bispecific antibody and polatuzumab vedotin is a CD79b-directed ADC (MMAE payload); this exploratory analysis compared tumor RNAseq and peripheral T-cell pharmacodynamics for Glofit-Pola (from NCT03533283; tumor RNAseq n=88) versus glofitamab monotherapy (from NCT03075696; tumor RNAseq n=147), using inverse probability weighting to approximate a matched 3L+ LBCL population. In the combo cohort, CR rates were reported across molecular subgroups including ABC 73.1%, DZsig+ 53.6%, and GCB DZsig− 57.7%, and across LymphoMAP archetypes including LN 70.4%, Tex 59.1%, and FMAC 59.0%; mechanistically, high proliferation signatures associated with shorter PFS on glofitamab mono (E2F HR 1.58 [95% CI 1.1–2.3]) but flipped direction on Glofit-Pola (E2F HR 0.62 [0.3–1.3]), while “immune-hot” tumors (high CD4/CD8 by xCell) predicted longer PFS on mono (CD4 HR 0.46 [0.3–0.8]) but not on combo (CD4 HR 1.60 [0.6–4.0]). Versus an important SOC benchmark in transplant-ineligible R/R DLBCL, pola-BR historically delivered CR rates on the order of ~40% (and BR alone far lower), while single-agent glofitamab in its pivotal program produced CRs in the ~35–40% range—so CRs in the ~54–73% band across these high-risk biology slices look directionally above typical monotherapy/chemo benchmarks, albeit here coming from cross-trial, biomarker-evaluable subsets rather than a randomized efficacy comparison.