Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a mature B cell neoplasm with t(11;14) cyclin D1 overexpression, usually advanced at diagnosis.

• Incidence 1 per 100,000, median age 65, male predominance.

• Variants: classic, leukaemic non-nodal (indolent, SOX11 negative), pleomorphic/blastoid (aggressive), with TP53 mutation, Ki-67 over 30%.

• MIPI score; high risk with TP53, blastoid morphology, complex karyotype.

• Extranodal: gastrointestinal tract (lymphomatous polyposis), marrow, spleen, CNS.

• Lymphadenopathy, splenomegaly, B symptoms, lymphocytosis, cytopenias, abdominal symptoms from bowel involvement.

• Some indolent, asymptomatic.

• Lymph node or tissue biopsy: CD5, CD19, CD20, cyclin D1, SOX11; FISH t(11;14).

• Ki-67, TP53 mutation and deletion, blastoid features.

• PET-CT, marrow, endoscopy with biopsies, LDH, beta-2 microglobulin, lumbar puncture in blastoid.

• Exclude CLL (CD23, cyclin D1 negative).

• Indolent leukaemic non-nodal disease: watch and wait.

• Younger fit patients: rituximab with cytarabine-based induction (R-CHOP/R-DHAP alternating, or Nordic MCL2) followed by autologous stem cell transplant and rituximab maintenance; BTK inhibitor combinations emerging (ibrutinib with rituximab).

• Older or transplant ineligible: bendamustine 90 mg/m2 days 1 and 2 with rituximab 375 mg/m2 for 6 cycles, followed by rituximab maintenance for 2 to 3 years (BR); BTK inhibitor with rituximab/bendamustine (acalabrutinib, ibrutinib).

• Relapse: BTK inhibitors (acalabrutinib 100 mg twice daily, zanubrutinib 160 mg twice daily, ibrutinib 560 mg daily), pirtobrutinib, venetoclax, lenalidomide-rituximab, bortezomib; CAR T-cell therapy (brexucabtagene autoleucel) for BTK failure; allogeneic transplant for TP53 aberrant disease.

• TP53 mutated: consider early CAR T or clinical trials.

• Supportive: tumour lysis prophylaxis, infections prophylaxis, monitoring for atrial fibrillation and bleeding with BTK inhibitors.