Treatment of Indolent Mantle Cell Lymphoma

Asymptomatic patients with indolent mantle cell lymphoma (MCL), a low burden of lymphadenopathy, and no significant splenomegaly or cytopenias may benefit from a watchful waiting approach. This approach has been demonstrated in several retrospective series.[1,2][Level of evidence C3] Because most patients with MCL are older than 60 years and MCL is not treated with curative intent, the quality-of life impact of treatment-related toxicities (both physical and financial) must be considered.

When patients with indolent MCL require therapy, a lower-intensity approach is preferred, but there is no standard approach due to the lack of clinical trials for this subgroup.

Induction chemotherapy regimens may be used for symptomatic progressive disease. These regimens range in intensity from rituximab alone to rituximab plus acalabrutinib (or ibrutinib or zanubrutinib), rituximab plus lenalidomide (R2), or bendamustine and rituximab (BR).

A prospective randomized trial included 373 patients with previously untreated MCL. A total of 87% of patients were aged 60 years or older. The study compared (1) BR versus BR plus bortezomib (BVR) as induction regimens and (2) rituximab versus R2 as maintenance regimens.[3]

Summary: BR induction therapy followed by maintenance therapy with rituximab remains a standard-of-care option. No benefit was noted in trials that incorporated early bortezomib or lenalidomide in the standard option. However, for many patients with indolent MCL, BR can be avoided by starting with rituximab alone and adding a Bruton tyrosine kinase inhibitor (such as acalabrutinib, ibrutinib, or zanubrutinib) if the response is not adequate after 4 to 8 weeks of therapy.