Summarize diffuse large B‑cell lymphoma (DLBCL) in MRCP style

Diffuse Large B-Cell Lymphoma (DLBCL) - MRCP Style Summary

Epidemiology & Risk Factors

DLBCL is the most common aggressive non-Hodgkin lymphoma, accounting for 30-58% of all NHL cases, with a crude European incidence of 3.8/100,000/year. 1

• The median age at diagnosis is 60-70 years, with incidence increasing dramatically with age (from 0.3/100,000 in ages 35-39 to 26.6/100,000 in ages 80-84) 2
• Male predominance is noted in most series 3
• Risk factors include: family history of lymphoma, autoimmune disease, HIV infection, HCV seropositivity, high body mass in young adulthood, and occupational exposures 1

Clinical Presentation

• Rapidly progressive lymphadenopathy (nodal or extranodal) is typical 4
• Extranodal involvement occurs in 30-40% of cases, most commonly stomach (20.79%) and bone marrow (10.89%) 3
• B symptoms (fever, night sweats, weight loss) present in approximately 42% of patients 3
• Bulky disease (>10 cm) occurs in approximately 10% of cases 3

Diagnosis

Surgical excisional biopsy sent unfixed to the laboratory is the gold standard for diagnosis, allowing assessment of nodal architecture and adequate material for phenotypic and molecular studies. 1

• Fine-needle aspirate should not be used as the sole diagnostic method 1
• Core needle or endoscopic biopsies are reserved only for patients where surgical approach is impractical or carries excessive risk 1

Essential Immunohistochemistry Panel

The minimum panel must include CD20, CD79a, BCL6, CD10, MYC, BCL2, Ki67, IRF4, CyclinD1, CD5, and CD23 to confirm B-cell lineage and exclude mimics. 1

• CD20 positivity is mandatory to confirm eligibility for rituximab-based therapy 5
• EBER-1 staining identifies EBV-positive DLBCL subtype in elderly patients 1
• PCR-based B-cell monoclonality testing should be considered when diagnostic confidence is reduced 1

Cell of Origin Classification

• Gene expression profiling distinguishes germinal center B-cell (GCB) from activated B-cell (ABC) subtypes 1
• GCB phenotype has significantly better clinical outcomes than ABC phenotype 1
• This classification is a major prognostic factor but does not currently alter standard first-line therapy 1

Staging Workup

PET-CT of chest, abdomen, and pelvis is strongly recommended over CT alone to better delineate disease extent and enable accurate response assessment. 5

• Bone marrow aspirate and biopsy are necessary 5
• LDH, complete blood count, comprehensive metabolic panel, HIV testing, and HCV serology are required 1

Risk Stratification

The International Prognostic Index (IPI) remains the most important tool for disease stratification and treatment planning. 6

IPI Score Components (1 point each):

• Age >60 years
• Stage III-IV disease
• Elevated LDH
• ECOG performance status ≥2

• 1 extranodal site

Risk Categories:

• Low risk (IPI 0-1): 5-year PFS 80-85% 7
• Low-intermediate risk (IPI 2)
• High-intermediate risk (IPI 3)
• High risk (IPI 4-5): 5-year PFS approximately 50% 7

First-Line Treatment

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) administered every 21 days for 6-8 cycles is the established standard of care with Category 1 evidence. 5

Standard R-CHOP Regimen:

• Rituximab 375 mg/m² IV Day 1
• Cyclophosphamide 750 mg/m² IV Day 1
• Doxorubicin 50 mg/m² IV Day 1
• Vincristine 1.4 mg/m² IV Day 1 (max 2 mg)
• Prednisone 100 mg PO Days 1-5
• Repeat every 21 days 5

Treatment Duration:

• 6-8 cycles depending on response and tolerability 5
• Young, low-risk patients (age <60, IPI 0-1) may receive de-escalated therapy with 4 cycles 8
• Patients with IPI ≥2 may benefit from polatuzumab vedotin-R-CHP over standard R-CHOP based on superior progression-free survival 8

Elderly Patients:

• Dose-reduced R-mini-CHOP or alternative regimens are used for patients unable to tolerate full-dose therapy 8

Critical Supportive Care Measures

Tumor lysis syndrome prophylaxis is mandatory given high tumor burden: aggressive hydration, allopurinol or rasburicase, and electrolyte monitoring. 5

• G-CSF should be used prophylactically to prevent febrile neutropenia 5
• PCP prophylaxis with trimethoprim-sulfamethoxazole is necessary, especially in HIV-positive patients 5
• HIV-positive patients should continue antiretroviral therapy throughout chemotherapy 5

CNS Prophylaxis

Intrathecal chemotherapy (cytarabine and/or methotrexate) is required for patients with high-risk features for CNS involvement. 5

High-Risk Features Requiring CNS Prophylaxis:

• Multiple extranodal sites (>1)
• HIV-positive status
• Testicular or orbital involvement
• High IPI score with elevated LDH 5

Consolidative Radiation

• Radiation therapy is reserved selectively for bulky or localized disease 5
• Should be considered for patients with bulky disease who did not achieve complete response after immunochemotherapy 7

Response Assessment

After 3-4 cycles, repeat PET-CT (preferred) or CT to assess response; complete the full 6-8 cycles if responding. 5

• PET-CT is highly recommended for accurate response evaluation over CT alone 5
• Residual masses are common and require PET-CT interpretation rather than size criteria alone 9

Relapsed/Refractory Disease

CAR T-cell therapy with axicabtagene ciloleucel or lisocabtagene maraleucel has replaced high-dose chemotherapy with autologous stem cell transplant (HDC/ASCT) as the standard for refractory disease or early relapse. 8

• HDC/ASCT should be considered for patients with chemotherapy-sensitive relapse who are not candidates for CAR T-cell therapy 7
• Glofitamab plus gemcitabine-oxaliplatin is a new standard for first relapse when CAR T-cell therapy is not feasible or as bridging before CAR T 8
• Additional options include: polatuzumab-bendamustine-rituximab, tafasitamab-lenalidomide, loncastuximab, and bispecific antibodies (glofitamab, epcoritamab, odronextamab) 8

Important Variants to Distinguish

Primary Mediastinal B-Cell Lymphoma (PMBCL):

• Occurs in young adults (median age 30-35) with female predominance (2:1) 9
• Presents as bulky anterior mediastinal mass with compartmentalizing fibrosis and "clear cells" 9
• DA-EPOCH-R is increasingly preferred over R-CHOP for younger, fit patients 9
• Radiation reserved only for PET-positive residual disease 9

Key Differential Diagnoses:

• Burkitt lymphoma
• Hodgkin lymphoma (especially in young patients with pruritus and mediastinal involvement) 2
• Plasmablastic lymphoma
• Blastic mantle cell lymphoma 1

Prognosis

• Overall 5-year PFS ranges from 50% (advanced disease) to 80-85% (limited disease) 7
• Survival has significantly improved in all European regions with rituximab-based therapy 1
• Adverse prognostic factors include: advanced age, high IPI score, ABC subtype, HIV-positive status, multiple extranodal sites, and B symptoms 5