Large B‐cell lymphoma (LBCL): EHA Clinical Practice Guidelines for diagnosis, treatment, and follow‐up

Abstract Large B‐cell lymphoma (LBCL) accounts for about one‐third of adult lymphoma cases. Diagnosis requires specialized hematopathology laboratories, with immunophenotypic analysis essential for confirming B‐cell lineage and identifying variants. MYC and BCL2 rearrangements indicate a poor prognosis. Staging and prognosis rely on positron emission tomography computed tomography (PET‐CT). The International Prognostic Index (IPI) aids risk stratification. PET‐CT is critical for assessing treatment response and guiding strategies. First‐line management for LBCL can be informed by interim PET to assess chemosensitivity, with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) or polatuzumab vedotin rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola‐R‐CHP) for advanced stages depending on IPI scores. Primary mediastinal B‐cell lymphoma (PMBCL) management favors R‐CHOP given every 14 days (R‐CHOP14) or dose‐adjusted etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and rituximab (DA‐EPOCH‐R) without radiotherapy in complete responders. Elderly patients, unfit or not (≥80 years or <80 with poor fitness), need geriatric assessment to guide therapy, often R‐miniCHOP or non‐anthracycline regimens. Frail patients should have adapted treatments. Prephase corticosteroids improve performance status, and supportive treatment should be optimized. The value of central nervous system (CNS) prophylaxis remains uncertain. CNS‐IPI scores and specific anatomical sites help identify high‐risk patients; magnetic resonance imaging (MRI) and colony‐stimulating factor (CSF) analysis are recommended. Approximately 30%–40% of patients with LBCL experience relapsed or refractory disease after 1L treatment. Treatment strategies vary based on the timing of relapse (<1 year or ≥1 year). For those refractory or relapsing within <1 year and fit for therapy, chimeric antigen receptor T (CART) are the gold standard in 2L. CART in CART‐naïve patients and bispecific antibodies appear to be the best approach in 3L. Follow‐up includes clinical examination for 2 years and management for long‐term side effects, such as cardiotoxicity, osteoporosis, immune dysfunction, neurocognitive impairment, endocrine dysfunction, fatigue, neuropathy, and mental distress.