P2, N=30, Not yet recruiting, Brown University

P2, N=35, Recruiting, The First Affiliated Hospital of Soochow University

P3, N=1130, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Dec 2027 --> Oct 2027

To achieve this, anthracycline-based chemotherapy in combination with rituximab is typically administered as initial therapy...In patients with the activated B-cell subtype of DLBCL, polatuzumab vedotin is commonly included in the combination...In patients ineligible for cellular therapy, or those who progress after CAR T-cell treatment, management is palliative and includes administration of bispecific antibodies or antibody drug conjugate combinations. To further improve the outcome of DLBCL patients, incorporation of cellular and bispecific therapies into front-line treatment is currently being tested.

P2, N=41, Recruiting, Jennifer Crombie, MD | Active, not recruiting --> Recruiting

Nonetheless, some patients experienced high-grade AEs or symptom recurrence and stopped BV/PV therapy. Future studies may provide clarification and guide clinical practice.

P1/2, N=68, Not yet recruiting, Sun Yat-sen University

Polatuzumab vedotin, an antibody-drug conjugate (ADC) targeting the B cell receptor (BCR) signaling subunit CD79B, has recently entered frontline therapy for diffuse large B cell lymphoma (DLBCL) and high-grade B cell lymphoma (HGBCL), achieving encouraging clinical results...Overall, our results uncover targetable vulnerabilities in MYC-driven B cell lymphomas, possibly extending to other aggressive B cell tumors silencing BCR expression. The data provide a rational basis for integrating CD79B-directed ADCs with mTOR or CDK4/6 inhibitors to prevent or overcome treatment resistance of aggressive B cell lymphomas.

P2, N=58, Recruiting, Tianjin Medical University Cancer Institute and Hospital

Recently, ADCs have expanded the DLBCL therapeutic landscape, with the approvals of CD79b-targeted polatuzumab vedotin and CD19-directed loncastuximab tesirine for R/R and even frontline disease. However, the clinical application of ADCs is accompanied by challenges, including the management of characteristic toxicities, understanding and overcoming mechanisms of resistance. This review systematically synthesizes the mechanisms of action, updated clinical evidence, toxicity profiles, and resistance mechanisms of ADCs in DLBCL, while also discusses management strategies and provides perspectives on future directions.

While novel therapies such as rituximab and polatuzumab vedotin have led to improved outcomes, approximately 35% of patients eventually develop relapsed or refractory disease. Among these, miR-155 and miR-21 are particularly well studied, playing central roles in both tumor progression and remodeling of the tumor microenvironment. This review summarizes current evidence on the biological and clinical relevance of miRNAs in DLBCL, emphasizing their diagnostic and prognostic potential.

P1, N=30, Suspended, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Recruiting --> Suspended | Trial primary completion date: Jun 2026 --> Jun 2027