What is the typical presentation and treatment approach for an older adult diagnosed with mantle cell lymphoma (MCL), a type of non-Hodgkin lymphoma (NHL)?

Mantle Cell Lymphoma: Clinical Overview

Disease Characteristics

Mantle cell lymphoma (MCL) is an aggressive, incurable B-cell non-Hodgkin lymphoma comprising approximately 6% of all NHL cases, with a median age at diagnosis of 67-70 years and a median overall survival of approximately 5 years despite treatment advances. 1

• Presentation: 75-80% of patients present with advanced stage III-IV disease at diagnosis, with frequent extranodal involvement particularly in bone marrow (present in most cases), peripheral blood, gastrointestinal tract, and occasionally skin 1
• Demographics: Male predominance (75-80% of cases), with the disease primarily affecting older adults 2
• Prognosis: Despite therapeutic advances including rituximab and intensive chemotherapy, MCL remains incurable with particularly poor outcomes in high-risk disease 1

Treatment Approach for Older Adults

Initial Assessment and Risk Stratification

Treatment selection must be based on patient fitness, disease biology (Ki-67, TP53 mutations, SOX11 status), and disease burden rather than age alone. 1

• Indolent disease criteria: SOX11-negative cases with leukemic non-nodal presentation, bone marrow-only involvement, splenomegaly, and Ki-67 <10% may warrant initial observation with close monitoring 1
• High-risk features: TP53 mutations, Ki-67 >30%, blastoid/pleomorphic variants, elevated LDH, or high MIPI score mandate immediate treatment 1, 3

First-Line Treatment for Older/Unfit Patients (≥65 years)

For elderly or unfit patients with symptomatic MCL, bendamustine-rituximab (BR) is the preferred first-line regimen, followed by rituximab maintenance therapy. 1, 4

• BR regimen: Demonstrated superior progression-free survival compared to R-CHOP (median PFS 35 vs 21 months) with better tolerability in older patients 3
• Alternative option: VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone) for patients who cannot receive bendamustine 1, 4
• R-CHOP alone: Should NOT be used as monotherapy in MCL as it is inadequate; however, when combined with rituximab maintenance, it provides acceptable outcomes in elderly patients 1

Maintenance Therapy

Rituximab maintenance significantly improves both progression-free survival and overall survival after induction therapy and should be administered every 2 months for up to 3 years. 1, 4

• Evidence base: Rituximab maintenance after R-CHOP demonstrated significant PFS and OS benefit with hazard ratio of 0.73 in patients ≥60 years 3
• Dosing: 375 mg/m² every 8 weeks until disease progression or for maximum 3 years 4, 3

Treatment for Younger Fit Patients (<65 years)

For younger fit patients, intensive cytarabine-containing immunochemotherapy followed by autologous stem cell transplantation (ASCT) with rituximab maintenance is the standard of care. 1, 4

• Preferred regimens: R-HyperCVAD alternating with high-dose methotrexate/cytarabine, or Nordic regimen (R-CHOP alternating with R-DHAP containing high-dose cytarabine) 1
• Consolidation: ASCT consolidation after cytarabine-containing induction significantly improves time to treatment failure (P=0.038) 1, 3
• Outcomes: Median overall survival of 13 years achievable with intensive approach in younger patients 5

Limited Stage Disease (Stage I-II)

For limited non-bulky stage I-II disease, shortened conventional chemotherapy (3-4 cycles) followed by consolidation radiotherapy (30-36 Gy involved field) is recommended. 1, 6

• Caveat: Only 5-10% of MCL patients present with truly localized disease; complete staging with PET/CT and bone marrow biopsy is essential to exclude occult advanced disease 1, 6
• Bulky or adverse features: Stage I-II patients with large tumor burden or high-risk features should receive systemic therapy as for advanced disease 1, 6

Relapsed/Refractory Disease

For relapsed or refractory MCL in older patients, targeted therapies including ibrutinib (BTK inhibitor), lenalidomide (immunomodulator), or venetoclax are preferred over repeat chemotherapy. 4, 7

• Ibrutinib: Highly efficacious in relapsed/refractory disease regardless of TP53 mutation status, well-tolerated in elderly patients 1, 7
• Lenalidomide: Effective immunomodulatory option with manageable toxicity profile 4, 5
• Repeat chemotherapy: Consider only for patients with late relapse (>2 years) without TP53 mutations 1

Critical Pitfalls to Avoid

• Never use rituximab monotherapy or radioimmunotherapy alone as these achieve only moderate response rates and are inadequate for MCL 1
• Never omit cytarabine from intensive regimens in younger fit patients, as it is the most critical component for improved outcomes 1, 3
• Never use R-CHOP alone without maintenance in elderly patients, as maintenance therapy is essential for optimal outcomes 1, 3
• Never assume localized disease without complete staging including PET/CT and bone marrow biopsy, as most MCL is advanced at presentation 1, 6
• Never apply "watch and wait" to typical MCL presentations; reserve observation only for confirmed indolent variants (SOX11-negative, Ki-67 <10%, no TP53 mutations) 1, 6