Mantle cell lymphoma (MCL) is an incurable, aggressive lymphoma that is typically associated with a poor prognosis. Because MCL is clinically heterogeneous, treatment should aim to maximize disease control while minimizing treatment-related toxicity. Recent developments, such as intensified induction with autologous stem cell transplantation (ASCT) consolidation for younger patients, have significantly improved outcomes, but a “one size fits all” approach to frontline treatment remains inadequate.

In an editorial article published in Expert Review of Hematology, Catherin Tang, MD, and John Kuruvilla, MD, of the division of medical oncology and hematology at the University of Toronto in Canada, summarized the current literature surrounding frontline management of MCL in various patient populations. They also discussed the employment of novel treatment strategies.1

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“There are still 2 broad categories of patients: transplant-eligible and nontransplant-eligible,” Dr Kuruvilla explained in an interview with Hematology Advisor. “For young, transplant-eligible patients, the challenges [include] how to integrate novel agents into first-line treatment and [whether we can avoid] transplant [in] patients based on minimal residual disease (MRD). For elderly, nontransplant-eligible patients, the standard of care is chemoimmunotherapy — either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or bendamustine and rituximab (BR) — together with rituximab maintenance. Novel agents, especially bortezomib, show promising results including survival advantages in these patient populations.” 

MCL is a mature B-cell neoplasm that constitutes 8% of all non-Hodgkin lymphomas (NHLs).1 It is typically disseminated at presentation, with a leukemic component in 20% to 30% of patients. The genetic hallmark of MCL is the chromosomal translocation t(11;14), which results in aberrant expression of cyclin D1. Several signaling pathways contribute to MCL pathogenesis, including the PI3K/AKT/mTOR pathway, which promotes tumor proliferation and survival, and the NF-kappa-B pathways.

The “watch and wait” treatment approach is appropriate for a small proportion of patients with MCL who have asymptomatic, low-bulk disease, as well as patients with leukemic, non-nodal MCL that is negative for SOX11. However, close follow-up is necessary for these patients because progression is inevitable. 

Anthracycline- and cytarabine-based chemoimmunotherapy followed by ASCT consolidation is the current standard of care for young, transplant-eligible patients with MCL. A European MCL Network prospective, randomized trial (MCL2) demonstrated progression-free survival (PFS) benefit (39 vs 17 months; P =.0108) but no overall survival (OS) benefit (83% vs 77%; P =.18) when comparing CHOP followed by myeloablative ASCT with interferon alfa maintenance.2

Achieving MRD with induction therapy has been demonstrated to be one of the strongest independent prognostic factors for response duration. Thus, intensifying induction with high-dose cytarabine prior to ASCT may improve outcomes. In another phase 3 trial from the European MCL Network, a treatment regimen consisting of R-CHOP or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP), ASCT, and consolidation with total body irradiation, melphalan, and cytarabine, yielded a median time to treatment failure of 9.1 years; the control group, which did not receive cytarabine, had a median time to treatment failure of 3.9 years.3