Lymphoma — Diffuse Large B-Cell (DLBCL) Clinical Trials

About Lymphoma — Diffuse Large B-Cell (DLBCL) trials

DLBCL trials are organized around two questions: cell of origin (germinal center B-cell or "GCB" vs activated B-cell or "ABC") and whether the tumor has a high-grade rearrangement profile. MYC rearrangement, BCL2 rearrangement, and BCL6 rearrangement are tested by FISH in most newly diagnosed DLBCL. Tumors with MYC plus BCL2 or BCL6 rearrangements are classified as high-grade B-cell lymphoma (HGBCL), often called "double-hit" or "triple-hit" lymphoma, and are treated and trialed differently from standard DLBCL. PD-L1 (CD274) is used in some immunotherapy trial designs, particularly for relapsed disease. Cell of origin (GCB vs non-GCB / ABC) is the other major prognostic axis, determined by IHC or NanoString rather than by the chip-level biomarkers, and gates several trials.

Most current DLBCL trial activity falls into treatment-line and disease-classification groups. Front-line trials test additions to or alternatives to R-CHOP, the standard backbone for most patients. Polatuzumab + R-CHP (Pola-R-CHP) is now standard for IPI ≥2 patients, and trials test further intensification or novel additions on top of these backbones. HGBCL (double-hit or triple-hit) trials use intensified backbones like DA-EPOCH-R and test novel agents in this aggressive subgroup. Second-line trials have shifted significantly with CAR-T cell therapy now standard for chemo-refractory or early-relapsed patients, and trials test new CAR products, allogeneic CAR-T, and CAR-T combinations. R/R trials beyond CAR-T test bispecific antibodies, novel ADCs, BTK and PI3K inhibitors, and immunotherapy combinations. Primary CNS lymphoma trials are a distinct trial set with their own backbones (high-dose methotrexate-based) and recruitment dynamics.

DLBCL trial coordinators typically ask about cell of origin, prior CAR-T exposure, and treatment line. Cell of origin (GCB vs non-GCB / ABC) gates many trials, especially second-line and beyond. Translocation status (MYC, BCL2, BCL6) for HGBCL-specific trials. Prior CAR-T exposure has become a major dividing line in R/R trials, with most trials now categorizing patients as CAR-T-naïve or post-CAR-T. Prior bispecific antibody exposure is becoming a similarly relevant criterion as bispecifics enter earlier lines. CD20 expression status for CD20-targeted trials. Most patients have prior rituximab exposure as part of R-CHOP, but CD20 negativity at relapse can affect eligibility. Performance status, with most trials accepting ECOG 0-2. CNS involvement: many trials require imaging clearance of CNS disease, while primary CNS lymphoma has its own dedicated trial set. Hepatitis B and C status is screened on most trials with implications for treatment.

Biomarkers tested in Lymphoma — Diffuse Large B-Cell (DLBCL) trials

These are the molecular markers most commonly required or evaluated in Lymphoma — Diffuse Large B-Cell (DLBCL) eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.