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.

Figure 1

Algorithm 1L large B‐cell lymphoma (LBCL) treatment. CNS, central nervous system; CT, computed tomography; DA‐EPOCH‐R, dose‐adjusted etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, rituximab; DS, Deauville Score; EOT, end of treatment; FDG‐PET, fluorodeoxyglucose‐positron emission tomography; HD‐MTX, high‐dose intravenous methotrexate; iPET, interim PET at 2, 3 or 4 cycles depending on local practice; IT‐MTX, intrathecal methotrexate; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PET, positron emission tomography; PMBCL, primary mediastinal B‐cell lymphoma; Pola‐R‐CHP, polatuzumab vedotin rituximab, cyclophosphamide, doxorubicin, and prednisone; PS, performance status; R‐ACVBP, rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, and prednisone; R‐CEOP, rituximab, cyclophosphamide, etoposide substituted for doxorubicin, vincristine, prednisone; R‐CHOEP‐14, R‐CHOP + etoposide every 14 days; R‐CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; R‐CHOP14, R‐CHOP given every 14 days; R‐CHOP21, R‐CHOP given every 21 days; R‐CODOX‐M/R‐IVAC, rituximab doxorubicin vincristine cyclophosphamide, IV methotrexate/etoposide, ifosfamide (with MESNA), cytarabine Intrathecal cytarabine intrathecal methotrexate; R‐COMP, RCHOP with non‐PEGylated liposomal doxorubicin; R‐GCVP, rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone; R‐GEMOX, rituximab, gemcitabine‐oxaliplatin; RT, radiotherapy; SUV standardized uptake value.

Figure 2

Algorithm. Treatment for large B‐cell lymphoma (LBLCL) in 2L and 3+L. ASCT, autologous stem cell transplant; CMR, complete metabolic response; CR, complete response; HDT, high ‐ dose therapy; IS‐RT, involved site radiotherapy; LDH, lactate dehydrogenase; Pola‐BR, polatuzumab vedotin, bendamustin, rituximab; PR, partial response; PS, performance status; R‐DHAX (P or C), rituximab, dexamethasone, cytarabine, and oxaliplatin (cisplatin or carboplatin); R‐ESHAP, rituximab, etoposide, cisplatin, and methylprednisolone; R‐GDP, rituximab, gemcitabine, dexamethasone, and cisplatin; R‐GemOx, rituximab, gemcitabine‐oxaliplatin; R‐ICE, rituximab, ifosfamide, carboplatin, and etoposide.