Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive blood cancer in adults. Standard chemotherapy cures roughly 60–70% of patients, but those who relapse or don't respond have historically had poor outcomes — a gap that CAR-T cell therapy has begun to close.
What's actually going on in research
CAR-T cell therapy targeting CD19 has become standard for second-line relapsed DLBCL and is now moving into first-line treatment for high-risk patients. Bispecific antibodies that redirect T-cells to kill CD20-positive lymphoma cells are showing strong responses as off-the-shelf alternatives. The molecular subtypes of DLBCL — GCB vs. ABC — respond differently to treatment, and subtype-directed trials are testing PI3K delta inhibitors, BTK inhibitors, and BCL-2 inhibitors for the harder-to-treat ABC subtype.
CAR-T cell therapy
Engineered T-cells targeting CD19 on DLBCL cells achieve durable remissions in relapsed patients and are moving into earlier lines of treatment for high-risk newly diagnosed disease.
Bispecific antibodies
Off-the-shelf T-cell engaging antibodies like epcoritamab and glofitamab bind both CD20 on lymphoma and CD3 on T-cells, producing responses without the need for cell manufacturing.
Subtype-directed therapy
The ABC subtype of DLBCL is more resistant to standard therapy; BTK inhibitors and BCL-2 inhibitors combined with chemotherapy are being tested specifically in this molecular subtype.
What to know before you search
Eligibility depends on DLBCL cell-of-origin subtype, IPI risk score, prior treatment history, and CD19 expression for CAR-T trials.
What types of trials are currently open
- Treatment trials — Testing new drug combinations, immunotherapy, or cell therapy for newly diagnosed or relapsed DLBCL.
- CAR-T trials — Evaluating CAR-T cell therapy in second-line and earlier settings, and novel CAR constructs.
- Consolidation trials — Testing whether stem cell transplant or maintenance therapy after remission improves outcomes.
- Elderly patient trials — Developing tolerable regimens for older adults who cannot receive full-dose immunochemotherapy.
- Biomarker trials — Using cell-of-origin and molecular profiling to match patients to targeted treatments.
Recently added Diffuse Large B-cell Lymphoma trials
A Clinical Study Exploring the Safety, Efficacy and Metabolic Kinetics of CT1182 Injection in Patients With Relapsed / Refractory Non Hodgkin Lymphoma
This study is a single arm, open label, dose exploring clinical study to evaluate the safety, efficacy, metabolic kinetics and pharmacodynamics of CT1182 cells in patients with relapsed / refractory B-cell non Hodgkin lymphoma (r/r B-NHL).
Pomalidomide, Anti-PD-1 Antibody Combined With Selinexor (PPS) in Relapsed/Refractory Primary Central Nervous System Diffuse Large B-Cell Lymphoma
Primary central nervous system diffuse large B-cell lymphoma (PCNSL-DLBCL) is a highly aggressive malignancy accounting for over 80% of primary CNS lymphomas, with an annual incidence of 0.4-0.6 per 100,000 people globally and a rising trend in immunocompetent patients. First-line high-dose methotrexate-based chemotherapy causes severe toxicities and nearly 50% of patients relapse within 1-2 years, developing relapsed/refractory (R/R) disease. Treatment options for R/R PCNSL are scarce, with low response rates, median survival of only 3-6 months, and 5-year survival below 5%. The blood-brain barrier and tumor heterogeneity further worsen outcomes. This prospective, multicenter, single-arm phase II study evaluates the efficacy and safety of pomalidomide, PD-1 inhibitor, and selinexor (PPS) in R/R PCNSL, aiming to provide a new effective treatment.
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