Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL) is the commonest aggressive non-Hodgkin lymphoma (30% of cases).

• Median age 65; subtypes: germinal centre B cell (GCB) and activated B cell (ABC) by cell of origin, double hit (MYC with BCL2 or BCL6) and double expressor, primary mediastinal B cell, primary CNS lymphoma.

• Prognostic score: IPI (age over 60, LDH, performance status, stage, extranodal sites over 1) and CNS-IPI.

• Cure with immunochemotherapy in about 60 to 70%.

• Complications: tumour lysis, CNS relapse (kidney/adrenal, high IPI), cytopenias.

• Rapidly growing nodal or extranodal mass (stomach, bowel, testis, bone, CNS), B symptoms, compressive symptoms (SVC syndrome, bowel obstruction).

• Raised LDH, hypercalcaemia, cytopenias.

• Excisional biopsy with immunohistochemistry (CD20, CD10, BCL6, MUM1, Ki-67, MYC, BCL2) and FISH for MYC, BCL2, BCL6 rearrangements.

• PET-CT, marrow when PET equivocal, LDH, HIV, hepatitis B/C.

• MRI brain and lumbar puncture in high CNS risk; echocardiography.

• Cell of origin classification by Hans algorithm or gene expression.

• Standard: R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 max 2 mg, prednisolone 100 mg days 1 to 5) every 21 days for 6 cycles; Pola-R-CHP (polatuzumab vedotin 1.8 mg/kg replacing vincristine) improves progression free survival for IPI 2 to 5.

• Limited stage: 3 to 4 cycles with involved site radiotherapy 30 to 36 Gy, or 6 cycles.

• Double hit: DA-EPOCH-R.

• CNS prophylaxis for high risk: high dose methotrexate 3 to 3.5 g/m2 for 2 to 4 cycles, or intrathecal methotrexate.

• Elderly frail: R-miniCHOP.

• Relapsed or refractory: salvage R-DHAP/R-ICE/R-GDP then autologous transplant if chemosensitive; CAR T-cell therapy (axicabtagene, lisocabtagene) second line for early relapse; bispecifics (glofitamab 2.5 mg step up to 30 mg, epcoritamab 48 mg); loncastuximab, polatuzumab-bendamustine-rituximab, tafasitamab-lenalidomide.

• Supportive: tumour lysis prophylaxis (allopurinol 300 mg, rasburicase 0.2 mg/kg for high burden), G-CSF, hepatitis B prophylaxis with entecavir 0.5 mg daily when HBsAg positive or core antibody positive, Pneumocystis prophylaxis, echocardiography monitoring.