Polivy (polatuzumab vedotin-piiq)

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.

Conventional platinum-based or gemcitabine- and bendamustine-containing regimens retain a role for short-term disease control but offer limited durability. In contrast, novel antibody-based therapies, including polatuzumab-containing combinations, loncastuximab tesirine, and tafasitamab plus lenalidomide, have expanded treatment options with improved tolerability. Most notably, CD20 × CD3 bispecific antibodies represent a major therapeutic advance, providing off-the-shelf immune engagement with predominantly outpatient administration. From a practical perspective, early identification of reversible barriers to CAR T-cell therapy and timely use of bispecific antibodies or other antibody-based regimens are critical to achieve rapid disease control, preserve organ function, and, when feasible, restore eligibility for cellular therapy.

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.

P1/2, N=122, Not yet recruiting, Sun Yat-sen University

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.