Mantle-Cell Lymphoma: Not Always Aggressive

For many years prior to immunophenotyping and detailed molecular characterization, mantle-cell lymphoma was identified as an indolent lymphoma and treated according to the paradigm of treatment intervention only when symptoms develop. The watch-and-wait paradigm for treatment of low-grade lymphoma is derived from many clinical trials demonstrating no benefit in terms of survival with early intervention. This contrasts with more aggressive lymphomas, in which treatment cures a subset of patients and improves survival. Identification of mantle-cell lymphoma as a distinct molecular diagnosis was followed by clinical studies, noting relatively short overall survival times as compared to other types of low-grade lymphoma. Mantle-cell lymphoma was re-classified as an aggressive lymphoma with many adapting an approach of treating the disease early, often with very aggressive therapies. Unfortunately, current treatment of mantle-cell lymphoma, including very aggressive approaches, still does not cure the disease. Breaking from this newly established paradigm of early treatment of mantle-cell lymphoma is challenging, however, since it has been adapted by many in practice and no published studies document the safety of the “old” watch-and-wait approach.

In this regard, Martin, Leonard, and colleagues from Weill Cornell Medical College – New York Presbyterian Hospital have reviewed their institutional experience, which includes a treatment philosophy of watching asymptomatic mantle-cell lymphoma patients without therapy until disease symptoms develop. They identified approximately a third of patients who could be managed in this manner with a subset not requiring therapy for a year or more. Examining clinical parameters, no measure of harm to this patient population was noted. Indeed, the asymptomatic group of patients had a significantly better survival rate than patients who were treated immediately. Many limitations arise from this trial, including the retrospective design and lack of randomization between early and delayed treatment that would allow definitive determination of the ideal treatment approach for this patient population. Given the low frequency of mantle-cell lymphoma and the small subset of patients who are asymptomatic, such a trial will likely never be performed.

This paper is very important because it provides published evidence that it is acceptable to monitor asymptomatic mantle-cell lymphoma patients without institution of therapy. For the asymptomatic patients with mantle-cell lymphoma, close observation without therapy can be viewed as an acceptable treatment choice based upon these data and lack of survival advantage or cure with currently available therapy.