What is the treatment for mantle cell lymphoma?

Treatment of Mantle Cell Lymphoma

The treatment of mantle cell lymphoma (MCL) requires a risk-stratified approach with chemoimmunotherapy as the backbone, followed by appropriate consolidation and maintenance therapy based on patient age, fitness, and disease characteristics. 1

Initial Assessment and Risk Stratification

• Evaluate patient age, fitness, comorbidities, and disease characteristics
• Assess Ki-67 proliferation index for prognostic assessment using MCL International Prognostic Index (MIPI-c) 2
• Consider SOX11 status and TP53 mutations which may influence disease aggressiveness 1
• Stage disease using Lugano classification (Stages I-IV) 1

Treatment Algorithm by Stage and Patient Characteristics

Stage I-II (Limited Disease)

• Early non-bulky disease: Shortened conventional chemotherapy induction followed by consolidation radiotherapy (30-36 Gy involved field) 1
• Bulky disease or adverse prognostic features: Treat as advanced stage disease with systemic therapy 1
• Note: Most early-stage patients relapse within 1 year despite localized treatment 1

Stage III-IV (Advanced Disease)

Indolent MCL (Asymptomatic, Low Tumor Burden)

• Consider "watch and wait" approach under close observation 1, 2
• Typically SOX11-negative disease with leukemic non-nodal presentation and low Ki-67 (<10%) 1

Symptomatic/High Tumor Burden Disease

For Younger/Fit Patients (<65 years):

1. Induction therapy: Cytarabine-containing regimen with rituximab 1, 2

   • R-CHOP alternating with R-high dose cytarabine
   • VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone) - showed improved PFS (31 months vs 16 months) compared to R-CHOP 2

2. Consolidation: High-dose therapy followed by autologous stem cell transplantation (ASCT) 1, 2

   • Total body irradiation (TBI) before ASCT beneficial for patients achieving only partial response 1

3. Maintenance: Rituximab maintenance (375 mg/m² every 8 weeks until disease progression) 2, 3

   • Significantly improves progression-free survival and overall survival 2

For Elderly/Less Fit Patients (≥65 years):

1. Induction therapy: Less intensive chemoimmunotherapy 1

   • Bendamustine plus rituximab (BR) - superior PFS (35 months vs 21 months) compared to R-CHOP 1, 2
   • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) 1
   • VR-CAP (bortezomib-containing regimen) 1

2. Maintenance: Rituximab maintenance (375 mg/m² every 8 weeks) 1, 2, 3

   • Significantly improves PFS and OS after R-CHOP 1

Relapsed/Refractory Disease

• Early relapse (<12-24 months): Use non-cross-resistant regimen 2

  • Targeted approaches: ibrutinib, lenalidomide, temsirolimus, bortezomib (preferably in combination with chemotherapy) 1, 4
  • Immunochemotherapy options: R-BAC (rituximab, bendamustine, cytarabine), BR 1

• Later relapse: Consider repeating previous therapy if long initial remission 1

• For eligible patients in remission after second-line therapy: Consider allogeneic stem cell transplantation 2

Treatment Outcomes and Prognosis

• Intensive immunochemotherapy with stem cell support can lead to long-term progression-free survival and potentially cure in younger patients 5
• The 6-year overall, event-free, and progression-free survival rates with intensive approaches can reach 70%, 56%, and 66%, respectively 5
• Ki-67 proliferation index is the strongest independent predictor of event-free survival 5

Important Considerations

• Avoid antibody monotherapy (rituximab alone) as it achieves only moderate response rates 1
• Prompt initiation of therapy is crucial for symptomatic patients or those with high tumor burden 1, 2
• Targeted therapies like BTK inhibitors (ibrutinib) are increasingly being incorporated into treatment regimens, especially for relapsed/refractory disease 4, 6
• Novel approaches including BCL2 inhibitors, T-cell engaging antibodies, and CAR T-cell therapy are being evaluated in clinical trials 6, 7