Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago.

In this episode, OncLive On Air® partnered with Two Onc Docs to deliver a comprehensive, board-focused review of diffuse large B-cell lymphoma (DLBCL) for 2026, updating their prior coverage to reflect several recent practice changes.

The discussion began with clinical presentation, emphasizing the classic B symptoms—weight loss, night sweats, fatigue, and fever—alongside painless, rapidly enlarging lymphadenopathy. They noted that approximately 30% to 40% of cases present with extranodal involvement (gastrointestinal, central nervous system [CNS], or thyroid) and stressed that an excisional biopsy is required, as fine-needle aspiration cannot preserve the architecture needed for histologic grading.

Turning to classification, Drs Armstrong and Tawagi reviewed germinal center vs non-germinal center origin, with non-germinal center disease carrying a worse prognosis. They characterized double-hit lymphoma, triple-hit lymphoma, and double-expressor lymphoma, the last conferring an intermediate prognosis.

Regarding workup, they recommended full-body PET scans, laboratory evaluation for tumor lysis syndrome, hepatitis B testing before anti-CD20 therapy, baseline echocardiography before anthracyclines, and lumbar puncture with intrathecal methotrexate in patients at high risk for CNS relapse. They also reviewed updated staging systems.

For treatment, they explained that limited-stage disease is now stratified by the stage-modified International Prognostic Index (IPI), guiding abbreviated vs full R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone). In advanced disease, 6 cycles of R-CHOP remains standard, with polatuzumab vedotin-piiq (Polivy) plus R-CHP (rituximab, cyclophosphamide, doxorubicin, and prednisolone) now a category 1 regimen for patients with an IPI of 2 or greater. They also addressed dose-adjusted regimens for double-hit disease, CAR T-cell therapy, and bispecific antibodies in the relapsed/refractory setting, as well as surveillance recommendations, cautioning against routine PET imaging.