Commentary (Armitage): Quality of Life in Low-Grade Non-Hodgkin’s Lymphoma

The management of patients with the less aggressive subtypes of non-Hodgkin’s lymphoma remains a clinical challenge. As pointed out by Webster and Cella, this challenge relates, at least in part, to the comparatively long median survival that can be achieved in such patients with a wide variety of treatment approaches. However, it is very important to realize that not all patients with the indolent varieties of non-Hodgkin’s lymphoma are the same.

New Classification of Lymphomas
Work by the International Lymphoma Study Group has stimulated a new way of thinking about the classification of the non-Hodgkin’s lymphomas.[1] Rather than focus on morphologically defined entities, the emphasis has shifted toward identifying more specific clinicopathologic entities-ie, real diseases. This new approach to classification takes into account biological (ie, genetic, immunologic, and so on) and clinical observations, in addition to cell size, shape, and growth pattern.

The new classification system will allow investigators to focus on specific illnesses for clinical studies. This work has led to the acceptance of a number of “new” lymphomas that previously were unrecognized. These newly recognized entities, such as mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphomas, and anaplastic large cell lymphoma, make up approximately 20% of all non-Hodgkin’s lymphomas (Table 1).[2]

Given this new, and I believe improved, approach to labeling lymphomas, the study of “low-grade” non-Hodgkin’s lymphomas becomes inappropriate. Rather, studies should focus on small lymphocytic lymphoma, follicular lymphoma, MALT lymphoma, and other specific lymphomas. Each of these illnesses has a different natural history and response to available therapies, and lumping them together risks missing important information.

Quality of Life Issues
The report by Webster and Cella focuses on data generated from patients with follicular lymphoma. This diagnosis represents 20% to 25% of all non-Hodgkin’s lymphomas diagnosed worldwide and more than 25% of those diagnosed in North America.[2] It is the best-studied indolent lymphoma and the disease to which most of their comments apply. However, follicular lymphoma is not a uniform disease, and all patients with this diagnosis should not be approached in the same way.

The development of the International Prognostic Index improved clinicians’ ability to subcategorize patients with diffuse large cell lymphoma.[3] However, it has become apparent that this system of predicting survival of patients with lymphoma applies to the less aggressive lymphomas as well as the more aggressive subtypes.

Follicular lymphoma is thought to have a good outlook because most patients have favorable risk factors in the International Prognostic Index and a prolonged survival. However, a subset of these patients have a number of adverse risk factors and a survival as poor as any subgroup of patients with aggressive lymphoma.[2] Certainly, these latter patients will require a different management approach.

Quality of life has been a difficult issue to study in patients with cancers, as well as other diseases. However, I believe that some points are clear. One fact that has been surprising to many clinicians is that, when asked, patients seem to value increased survival over any other factor and are willing to accept surprising risks to achieve modest increases in survival. This leads back to the most frustrating question in the management of patients with follicular lymphoma: Does any therapy significantly modify the course of the illness?

Unfortunately, we have no completed, randomized trials to help answer this important question. In particular, no randomized trial comparing therapy to no therapy has been conducted. I doubt that any clinician who cares for patients with lymphoma questions the positive effect of treatment on their clinical course, although treatment can be withheld in many patients until symptoms develop. The debate centers on the timing of therapy and the relative merits of more vs less intensive approaches.

The management of indolent lymphomas, such as follicular lymphoma, is likely to remain a source of controversy for many years. Until definitive answers are available, this field remains one where the art of practicing medicine is still extremely important.

References:

1. Harris NJ, Jaffe ES, Stein H, et al: A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 84:1361, 1994.

2. Evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood 89:3909, 1997.

3. Project: A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 329:987, 1993.